Formulation for protection against oxidative stress containing benzofuranone derivatives

ABSTRACT

The invention relates to a cosmetic or pharmaceutical formulation comprising at least one compound of formula (I). The cosmetics or pharmaceutical products are particularly suitable for the care of the skin in protecting against oxidative stress and ageing phenomena.

[0001] The present invention relates to cosmetic or pharmaceuticalformulations and foods and food supplements which have improvedprotection against oxidation. The invention furthermore relates to novelcompounds having antioxidative properties and to their use asantioxidants.

[0002] A certain degree of tanning of the skin is regarded in modernsociety as attractive and as an expression of vigour and sportiness. Inaddition to this desired action of the sun on the skin, a number ofundesired side effects occur, such as sunburn or premature skin ageingand wrinkling. A number of effective UV filters have now been developedwhich, applied to the skin in the form of creams, lotions or gels, areable effectively to prevent the development of sunburn, even in the caseof relatively great exposure to the sun. The UV filters present in thepharmaceutical or cosmetic preparation form a film or layer on thesurface of the skin and do not penetrate into deeper skin layers withfurther care substances present in the preparation. Known UV filters andsunscreens thus only act by absorbing certain regions of the sunlight,preventing this radiation from penetrating into deeper layers of theskin. As is known, the most dangerous part of solar radiation is formedby ultraviolet rays having a wavelength of less than 400 nm. The lowerlimit for the ultraviolet rays which reach the earth's surface isrestricted to about 280 nm by absorption in the ozone layer. Thesun-protection filters usual today in cosmetics absorb in a wavelengthrange from 280 to 400 nm. This range covers UV-B rays having awavelength of between 280 and 320 nm, which play a crucial role in theformation of solar erythema, and also UV-A rays, having a wavelength ofbetween 320 and 400 nm, which tan the skin, but also allow ageing,favour the triggering of an erythematous reaction or can exacerbate thisreaction in certain people or even trigger phototoxic or photoallergicand irritative reactions.

[0003] Skin damage is not caused just by sunlight, but also by otherexternal influences, such as cold or heat. Furthermore, the skinundergoes natural ageing, with the formation of wrinkles and a reductionin the elasticity of the skin.

[0004] The object of care cosmetics is wherever possible to obtain theimpression of youthful skin. In principle, there are various ways ofachieving this object. For example, existing skin damage, such asirregular pigmentation or the development of wrinkles, can becompensated for by covering powders or creams. Another approach is toprotect the skin against environmental influences which lead topermanent damage and thus ageing of the skin. The idea is therefore tointervene in a preventative manner and thus to delay the ageing process.One example of this is the UV filters already mentioned, which, as aresult of absorption of certain wavelength ranges, prevent or at leastreduce skin damage. Whereas in the case of UV filters the damagingevent, the UV radiation, is screened off by the skin, another routeinvolves attempting to support the skin's natural defence or repairmechanisms against the damaging event. Finally, a further approachinvolves compensating for the weakening defence functions of the skinagainst harmful influences with increasing age by externally supplyingsubstances which are able to replace this diminishing defence or repairfunction. For example, the skin has the ability to scavenge freeradicals formed by external or internal stress factors. This abilitydiminishes with increasing age, causing the ageing process to acceleratewith increasing age.

[0005] It must be possible for substances which are intended to supportor replace defence or repair functions of the skin to be transported totheir site of action. Two methods are in principle available for thispurpose: either the substance is applied to the skin and penetratesthrough the outer layers into deeper layers of the skin or the activeingredient is, for example after oral intake, transported to the site ofaction via the bloodstream.

[0006] A further difficulty in the preparation of cosmetics is thatactive ingredients which are intended to be incorporated into cosmeticformulations are frequently unstable and can be damaged in theformulation. The damage may be caused, for example, by a reaction withatmospheric oxygen or by absorption of UV rays. The molecules damaged inthis way may, for example, change their colour and/or lose theiractivity through their structural change.

[0007] DE 197 10 854 A1 describes the use of benzophenones and theirderivatives against UV-induced decomposition of dibenzoylmethane and itsderivatives. [DE 197 46 654 A1 describes cosmetic and pharmaceuticalpreparations comprising photostable UV filters. 4,4-Diarylbutadienes areused here as photostable UV filters in cosmetic and pharmaceuticalpreparations for protecting the human skin or human hair againstsunlight, alone or together with compounds which absorb in the UV regionand which are known per se for cosmetic and pharmaceutical preparations.

[0008] DE 195 08 608 A1 describes a light-stable cosmetic composition.Cosmetic compositions are disclosed for protection against UV rayshaving a wavelength of between 280 and 400 nm which comprise at leastone tetraalkylquercetin in a cosmetically acceptable, oil-based medium.

[0009] DE 197 55 504 A1 describes the use of flavones and flavonoidsagainst UV-induced decomposition of dibenzoylmethane and itsderivatives.

[0010] DE 197 50 030 A1 describes a cosmetic preparation comprisingbutylmethoxydibenzoylmethane as light-protection filter. In order toimprove the photostability, insoluble inorganic particles which absorbin the UVA region are added to the cosmetic preparation. The insolubleinorganic particles used are microfine particles selected from the groupconsisting of titanium dioxide, iron oxide, cerium oxide and zinc oxide.

[0011] U.S. Pat. No. 4,532,257 describes substituted coumaranones inwhich the benzofuran moiety is either unsubstituted or carries acarboxyl group and an alkyl or alkenyl group. Various substituents aredescribed for the benzyl group. The compounds are proposed asantiallergic or antiinflammatory active ingredients, in particular forthe treatment of asthma.

[0012] GB 2,131,431 describes coumaranone derivatives which may besubstituted, inter alia, by C₁₋₄-alkoxy groups. The compounds arelikewise proposed for the treatment of allergic or inflammatorydiseases.

[0013] WO 91/17749 proposes growth inhibitors for the treatment ofcancer. Amongst the compounds proposed are aurones, in which the basicskeleton may be substituted by hydroxyl or methoxy groups.

[0014] FR 1 502 727 describes the preparation ofaryl-2-amino-3-benzofuran and of aryl-2-benzo-3(2H)-furanone.

[0015] The object of the invention is therefore to provide a cosmetic orpharmaceutical composition which has a protective action against UV raysand/or exerts a protective action against oxidative stress on body cellsand/or counters ageing of the skin.

[0016] This object is achieved by a cosmetic or pharmaceuticalformulation comprising at least one compound of the formula I

[0017] in which —X— is a single bond, —CH₂—, ═CH—, —C(O)—, ═C(OR⁵)—,—C(NR⁵)—, —CH(NR⁵R⁶)— or —CH(OR⁵)—, and R¹, R², R³, R⁴, R⁵ and R⁶ may beidentical or different and are, independently of one another,

[0018] H

[0019] straight-chain or branched C₁- to C₁₂-alkyl and/or alkylcarbonylgroups,

[0020] straight-chain or branched C₃- to C₁₂-alkenyl and/or-alkenylcarbonyl groups,

[0021] straight-chain or branched C₁- to C₁₂-hydroxyalkyl groups, inwhich the hydroxyl group may be bonded to a primary or secondary carbonatom of the chain, and furthermore the alkyl chain may also beinterrupted by oxygen,

[0022] C₃- to C₁₀-cycloalkyl and/or cycloalkylcarbonyl groups and C₃- toC₁₂-cycloalkenyl and/or cycloalkenylcarbonyl groups, in which each ofthe rings may also be bridged by —(CH₂)_(n)— groups, where n=from 1 to3,

[0023] aryl and/or arylcarbonyl groups,

[0024] heteroaryl and/or heteroarylcarbonyl groups, where these groupsmay be substituted by alkyl, hydroxyl, alkoxy, amino, mono- anddi-alkylamino, sulfonic acid, carboxyl and/or halogen groups,

[0025] mono- and/or oligoglycosyl radicals,

[0026] in which Me is a proton or an alkali metal ion, in particular asodium or potassium ion.

[0027] The radicals may thus be bonded to the basic structure as ethersor as esters.

[0028] The positive action of the cosmetic or pharmaceutical preparationaccording to the invention is presumably based on the action of thecompounds of the formula I as antioxidants or as free-radicalscavengers. In order to be able to develop their positive action on theskin, it should be possible for the compounds of the formula I topenetrate into deeper skin layers. A number of possibilities areavailable for this purpose. Firstly, the compounds of the formula I mayhave adequate lipophilicity in order to be able to penetrate the outerskin layer into epidermal layers. As a further possibility,corresponding transport agents, for example liposomes, which facilitatetransport of the compounds of the formula I through the outer skinlayers, may also be provided in the preparation. Finally, systemictransport of the compounds of the formula I is also conceivable. In thiscase, the preparation is designed in such a way, for example, that it issuitable for oral administration.

[0029] In general, the substances of the formula I act as free-radicalscavengers. Free radicals of this type are not only produced bysunlight, but are also formed under various conditions. Examples areanoxia, which blocks the electron flow upstream of the cytochromeoxidases and causes the formation of superoxide free-radical anions;inflammation which is associated, inter alia, with the formation ofsuperoxide anions by the membrane NADPH oxidase of the leukocytes, butwhich is also associated with the formation (by disproportionation inthe presence of iron(II) ions) of the hydroxyl free radicals and otherreactive species which are normally involved in the phenomenon ofphagocytosis; and lipid autooxidation, which is generally initiated by ahydroxyl free radical and produces lipidic alkoxy free radicals andhydroperoxides.

[0030] It is assumed that the compounds of the formula I also act asenzyme inhibitors. They are thought to inhibit histidine decarboxylase,protein kinases, elastase, aldose reductase and hyaluronidase, andtherefore enable the intactness of the basic substance of vascularsheaths to be maintained. Furthermore, they are thought to inhibitcatechol O-methyltransferase in a non-specific manner, increasing theamount of available catecholamines and thus the vascular strength.Furthermore, they inhibit AMP phosphodiesterase, providing thesubstances with potential for inhibiting thrombocyte aggregation.

[0031] Owing to these properties, the formulations according to theinvention or the compounds according to the invention are generallysuitable for immunoprotection and for DNA and RNA protection. Inparticular, the formulations and compounds are suitable for protectingDNA and RNA against oxidative attacks, against free radicals and againstdamage by radiation, in particular UV radiation. A further advantage ofthe formulations according to the invention and the compounds accordingto the invention is cell protection, in particular protection ofLangerhans cells, against damage by the above-mentioned influences. Allthese uses are expressly also a subject-matter of the present invention.

[0032] For the purposes of the invention, preference is given tocosmetic or pharmaceutical formulations which comprise compounds of theformula I in which —X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—,—C(NR⁵)—, —CH(NR⁵R⁶)— or —CH(OR⁵)—.

[0033] Preference is furthermore given to cosmetic or pharmaceuticalformulations which comprise compounds of the formula I in which —X—is═CH— and at least one radical from R¹, R², R³ and R⁴ is a group selectedfrom the following list:

[0034] straight-chain or branched C₁- to C₁₂-alkylcarbonyl groups,

[0035] straight-chain or branched C₃- to C₁₂-alkenylcarbonyl groups,

[0036] straight-chain or branched C₁- to C₁₂-hydroxyalkyl groups, inwhich the hydroxyl group may be bonded to a primary or secondary carbonatom of the chain, and furthermore the alkyl chain may also beinterrupted by oxygen,

[0037] C₃- to C₁₀-cycloalkylcarbonyl groups and C₃- to C₁₂-cycloalkenyland/or cycloalkenylcarbonyl groups, in which each of the rings may alsobe bridged by —(CH₂)_(n)— groups, where n=from 1 to 3,

[0038] aryl and/or arylcarbonyl groups,

[0039] heteroaryl and/or heteroarylcarbonyl groups, where these groupsmay be substituted by alkyl, hydroxyl, alkoxy, amino, mono- anddi-alkylamino, sulfonic acid, carboxyl and/or halogen groups,

[0040] mono- and/or oligoglycosyl radicals,

[0041] in which Me is a proton or an alkali metal ion, in particular asodium or potassium ion.

[0042] The basic structure 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-onehas very good properties. This corresponds to the compound of theformula I in which X═—CH₂— and R¹═R²═R³═R⁴═H. The potential of thiscompound as antioxidant and free-radical scavenger, in particular whenused in cosmetics, pharmaceuticals and foods, has not been recognisedhitherto. This also applies to 4,6,3′,4′-tetrahydroxyaurone, whichcorresponds to a compound of the formula I in which X══CH—, andR¹═R²═R³═R⁴═H. This opens up the route to a new class of antioxidantswhich arises through variation of the substituents R¹, R², R³ and R⁴.Thus, for example, the solubility in water or oils can be matched to therespective need by replacing one or more protons in the hydroxyl groupsof the basic structures by, for example, alkyl groups, cycloalkyl groupsor -alkenyl groups. These substituents may in turn be modified in theirproperties by substituents, such as, for example, hydroxyl groups oramino groups, which may in turn be alkylated. The solubility in watermay be improved by, for example, selecting the radicals R¹, R², R³ andR⁴ as sulfate or phosphate groups. A mixture of mono-, di- andtrisulfate, referred to below as “sulfated coumaranone”, is particularlysuitable. Particular emphasis is placed on the trisulfate (X═—CH₂—;R¹═R³═R⁴═SO₃Me, R²═H), which is represented by the following formula:

[0043] The oil solubility can be improved by, for example, esterifyingthe hydroxyl groups of the basic structures using ethylhexanecarboxylicacid.

[0044] Further suitable radicals are obtained by esterification withmonocarboxylic acids, such as butyric acid, valeric acid, hexanoic acid,sorbic acid, ascorbic acid or lauric acid. These radicals promotetransport of the compound through biological membranes. The basicstructure can then be liberated in the cell by cleaving off thecarboxylic acids by means of esterases.

[0045] A further particularly interesting class of compounds arises ifthe basic structures, which here are preferably taken to mean the basicstructures in which X is a single bond, —CH₂— or ═CH—, andR¹═R²═R³═R⁴═H, are substituted by UV-absorbent groups. The compounds andformulations comprising these compounds then advantageously exhibit aprotective action as antioxidants and as UV filters. Even the basicstructures exhibit a protective action against UVA radiation. By meansof suitable radicals R¹, R², R³ and R⁴, UVA/B broad-band filters cantherefore be provided.

[0046] The groups here are advantageously selected in such a way thatthey exhibit, in particular, an absorption maximum in the wavelengthranges of UVA and UVB radiation which are particularly harmful for theskin. The UV-B content of sunlight covers the range from 280 to 320 nmand UV-A radiation covers the range >320 nm, which is directly adjacentto the region of visible light.

[0047] Preference is also given to structures in which at least one ofthe radicals R¹, R², R³ and R⁴ is formed by a mono- or oligosaccharide.Preference is given here to hexosyl radicals, in particular ramnosylradicals and glycosyl radicals. However, other hexosyl radicals, forexample allosyl, altrosyl, galactosyl, gulosyl, idosyl, mannosyl andtalosyl, may also advantageously be used. It may also be advantageous touse pentosyl radicals. The glycosyl radicals may be linked to the basicstructure by means of an α- or β-glycosidic link. A preferreddisaccharide is, for example,6-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside.

[0048] Aurone (R¹═R²═R³═R⁴═H, X══CH—) belongs to the class of thebioflavonoids. The term bioflavonoids here is taken to mean naturallyoccurring flavonoids.

[0049] 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one is accessible, forexample, from quercetin by reaction of quercetin with sodium dithionitein aqueous solution. It differs from bioflavonoids through thefive-membered ring of the benzofuranone.

[0050] Another way of preparing4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one proceeds, as described inBritish Patent GB 2,131,431, via aurone. Aurone can also be preparedsynthetically here. This is described, for example, in British Patent GB2,030,142.

[0051] Variation of the group designated by X in the formula I givesrise to a broader area of compounds. Through incorporation of a carbonylgroup —C(O)—, the wavelength of the UV absorption can be modified.Through incorporation of a hydroxyl or amino function, further linkagepoints, for example, are available for modification of the compounds ofthe formula I.

[0052] The formulations according to the invention usually comprise thecompound of the formula I in amounts of 0.01-10% by weight. Theseamounts ensure that the compound of the formula I results in theformulation according to the invention having the stated properties. Ifparticular requirements are to be made of the formulation, however, theformulation may also comprise the compound of the formula I in differingamounts. It is particularly preferred for the compound of the formula Ito be present in the formulations according to the invention in amountsof 0.02-5% by weight, with formulations comprising 0.05-0.2% by weightof the compound of the formula I having proven particularlyadvantageous.

[0053] The protective action against UV radiation can be improved if theformulation comprises one or more UV filters.

[0054] In principle, all UV filters are suitable for a combination.Particular preference is given to UV filters whose physiologicalacceptability has already been demonstrated. There are many provensubstances which are known from the specialist literature both for UVAand UVB filters, for example

[0055] benzylidenecamphor derivatives, such as

[0056] 3-(4′-methylbenzylidene)-dl-camphor (for example Eusolex® 6300),

[0057] 3-benzylidenecamphor (for example Mexoryl® SD),

[0058] polymers of N-{(2 and4)-[(2-oxoborn-3-ylidene)methyl]benzyl}acrylamide (for example Mexoryl®SW),

[0059] N, N, N-trimethyl-4-(2-oxoborn-3-ylidenemethyl)aniliniummethylsulfate (for example Mexoryle® SK) or

[0060] α-(2-oxoborn-3-ylidene)toluene-4-sulfonic acid (for exampleMexoryl® SL),

[0061] benzoyl- or dibenzoylmethanes, such as

[0062] 1 -(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane- 1,3-dione(for example Eusolex® 9020) or

[0063] 4-isopropyldibenzoylmethane (for example Eusolex® 8020),

[0064] benzophenones, such as

[0065] 2-hydroxy-4-methoxybenzophenone (for example Eusolex® 4360) or

[0066] 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodiumsalt (for example Uvinul® MS-40),

[0067] methoxycinnamic acid esters, such as

[0068] octyl methoxycinnamate (for example Eusolex® 2292),

[0069] isopentyl 4-methoxycinnamate, for example as a mixture of theisomers (for example Neo Heliopan® E 1000),

[0070] salicylate derivatives, such as

[0071] 2-ethylhexyl salicylate (for example Eusolex® OS),

[0072] 4-isopropylbenzyl salicylate (for example Megasol®) or

[0073] 3,3,5-trimethylcyclohexyl salicylate (for example Eusolex® HMS),

[0074] 4-aminobenzoic acid and derivatives, such as

[0075] 4-aminobenzoic acid,

[0076] 2-ethylhexyl 4-(dimethylamino)benzoate (for example Eusolex®6007),

[0077] ethoxylated ethyl 4-aminobenzoate (for example Uvinul® P25),

[0078] and further substances, such as

[0079] 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (for example Eusolex®OCR),

[0080] 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodiumand triethanolamine salts (for example Eusolex® 232),

[0081]3,3′-(1,4-phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo[2.2.1]-hept-1-ylmethanesulfonicacid and its salts (for example Mexoryl® SX) and

[0082] 2,4,6-trianilino-(p-carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine(for example Uvinul® T 150).

[0083] The compounds mentioned in the list should only be regarded asexamples. It is of course also possible to use other UV filters.

[0084] These organic UV filters are generally incorporated into cosmeticformulations in an amount of from 0.5 to 10 per cent by weight,preferably 1-8%. Further suitable organic UV filters are, for example,

[0085]2-(2H-benzotriazol-2-yl)4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1-(trimethylsilyloxy)disiloxanyl)propyl)phenol (for exampleSilatrizole®),

[0086] 2-ethylhexyl4,4′-[(6-[4-((1,1-dimethylethyl)aminocarbonyl)phenyl-amino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate)(for example Uvasorb® HEB),

[0087] α-(trimethylsilyl)-ω-[trimethylsilyl)oxy]poly[oxy(dimethyl [andapproximately 6% ofmethyl[2-[p-[2,2-bis(ethoxycarbonyl]vinyl]phenoxy]-1-methyleneethyl] andapproximately 1.5% ofmethyl[3-[p-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy]propenyl] and from 0.1to 0.4% of (methylhydrogen]silylene]] (n≈60) (CAS No. 207 574-74-1)

[0088]2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol)(CAS No. 103 597-45-1)

[0089] 2,2′-(1,4-phenylene)bis(1H-benzimidazole-4,6-disulfonic acid,monosodium salt) (CAS No. 180 898-37-7) and

[0090]2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine(CAS No. 103 597-45-, 187 393-00-6).

[0091] These organic UV filters are generally incorporated into cosmeticformulations in an amount of from 0.5 to 20 per cent by weight,preferably 1-15%.

[0092] Conceivable inorganic UV filters are those from the groupconsisting of titanium dioxides, such as, for example, coated titaniumdioxide (for example Eusolex® T-2000, Eusolex® T-AQUA), zinc oxides (forexample Sachtotec®), iron oxides and also cerium oxides. These inorganicUV filters are generally incorporated into cosmetic formulations in anamount of from 0.5 to 20 per cent by weight, preferably 2-10%.

[0093] Preferred compounds having UV-filtering properties are3-(4′-methylbenzylidine)-dl-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium andtriethanolamine salts.

[0094] The protective action against the damaging effects of UVradiation can be optimised by combining one or more compounds of theformula I with further UV filters.

[0095] The combination of the above-mentioned UV filters with a compoundof the formula I in a formulation then gives rise to a composition whichcombines light protection with particular skin friendliness. Thecombination of UV filters with compounds of the formula I incompositions of this type usually takes place in ratios in the rangefrom 100 000:1 to 1:10, preferably in amounts of from 1000:1 to 1:10.

[0096] The protective action against oxidative stress or against theeffect of free radicals can be further improved if the formulationcomprises one or more further antioxidants.

[0097] There are many proven substances known from the specialistliterature which can be used, for example amino acids (for exampleglycine, histidine, tyrosine, tryptophan) and derivatives thereof,imidazoles (for example urocanic acid) and derivatives thereof,peptides, such as D,L-carnosine, D-carnosine, L-carnosine andderivatives thereof (for example anserine), carotinoids, carotenes (forexample α-carotene, β-carotene, lycopene) and derivatives thereof,chlorogenic acid and derivatives thereof, lipoic acid and derivativesthereof (for example dihydrolipoic acid), aurothioglucose,propylthiouracil and other thiols (for example thioredoxin, glutathione,cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl,propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl,cholesteryl and glyceryl esters thereof), and salts thereof, dilaurylthiodipropionate, distearyl thiodipropionate, thiodipropionic acid andderivatives thereof (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts), and sulfoximine compounds (for examplebuthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones,penta-, hexa- and heptathionine sulfoximine) in very low tolerated doses(for example pmol to μmol/kg), and also (metal) chelating agents, (forexample α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin),α-hydroxy acids (for example citric acid, lactic acid, malic acid),humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTAand derivatives thereof, unsaturated fatty acids and derivativesthereof, vitamin C and derivatives (for example ascorbyl palmitate,magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols andderivatives (for example vitamin E acetate), vitamin A and derivatives(for example vitamin A palmitate), and coniferyl benzoate of benzoinresin, rutinic acid and derivatives thereof, α-glycosyl rutin, ferulicacid, furfurylidineglucitol, carnosine, butylhydroxytoluene,butylhydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone,quercetin, uric acid and derivatives thereof, mannose and derivativesthereof, zinc and derivatives thereof (for example ZnO, ZnSO₄), seleniumand derivatives thereof (for example selenomethionine), stilbenes andderivatives thereof (for example stilbene oxide, trans-stilbene oxide).

[0098] Mixtures of antioxidants are likewise suitable for use in thecosmetic formulations according to the invention. Known and commercialmixtures are, for example, mixtures comprising, as active ingredients,lecithin, L-(+)-ascorbyl palmitate and citric acid (for example Oxynex®AP), natural tocopherols, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acidand citric acid (for example Oxynex® K LIQUID), tocopherol extracts fromnatural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid andcitric acid (for example Oxynex® L LIQUID), DL-α-tocopherol,L-(+)-ascorbyl palmitate, citric acid and lecithin (for example Oxynex®LM) or butylhydroxytoluene (BHT), L-(+)-ascorbyl palmitate and citricacid (for example Oxynex® 2004). Anti-oxidants of this type are usuallyemployed with compounds of the formula I in compositions of this type inratios in the range from 1000:1 to 1:1000, preferably in amounts of from100:1 to 1:100.

[0099] The formulations according to the invention may comprise vitaminsas further ingredients. The cosmetic formulations according to theinvention preferably comprise vitamins and vitamin derivatives selectedfrom vitamin A, vitamin A propionate, vitamin A palmitate, vitamin Aacetate, retinol, vitamin B, thiamine chloride hydrochloride (vitaminB₁), riboflavin (vitamin B₂), nicotinamide, vitamin C (ascorbic acid),vitamin D, ergocalciferol (vitamin D₂), vitamin E, DL 60 -tocopherol,tocopherol E acetate, tocopherol hydrogen-succinate, vitamin K₁, esculin(vitamin P active ingredient), thiamine (vitamin B₁), nicotinic acid(niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B₆),panthothenic acid, biotin, folic acid and cobalamine (vitamin B₁₂),particularly preferably vitamin A palmitate, vitamin C, DL-α-tocopherol,tocopherol E acetate, nicotinic acid, panthothenic acid and biotin.Vitamins are usually employed here with compounds of the formula I inratios in the range from 1000:1 to 1:1000, preferably in amounts of from100:1 to 1:100.

[0100] The formulations according to the invention may in additioncomprise further conventional skin-protecting or skin-care activeingredients. These may in principle be any active ingredients known tothe person skilled in the art.

[0101] Particularly preferred active ingredients arepyrimidinecarboxylic acids and/or aryl oximes.

[0102] Pyrimidinecarboxylic acids occur in halophilic microorganisms andplay a role in osmoregulation of these organisms (E. A. Galinski et al.,Eur. J. Biochem., 149 (1985) pages 135-139). Of the pyrimidinecarboxylicacids, particular mention should be made here of ectoin((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) andhydroxyectoin((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid) and their derivatives. These compounds stabilise enzymes and otherbiomolecules in aqueous solutions and organic solvents. Furthermore,they stabilise, in particular, enzymes against denaturing conditions,such as salts, extreme pH values, surfactants, urea, guanidiniumchloride and other compounds.

[0103] Ectoin and ectoin derivatives, such as hydroxyectoin, canadvantageously be employed in medicaments. In particular, hydroxyectoincan be employed for the preparation of a medicament for the treatment ofskin diseases. Other areas of application of hydroxyectoin and otherectoin derivatives are typically in areas in which, for example,trehalose is used as additive. Thus, ectoin derivatives, such ashydroxyectoin, can be used as protectant in dried yeast and bacteriacells. Pharmaceutical products, such as non-glycosylated,pharmaceutically active peptides and proteins, for example t-PA, canalso be protected with ectoin or its derivatives.

[0104] Of the cosmetic applications, particular mention should be madeof the use of ectoin and ectoin derivatives for the care of aged, dry orirritated skin. Thus, European Patent Application EP-A-0 671 161describes, in particular, that ectoin and hydroxyectoin are employed incosmetic preparations, such as powders, soaps, surfactant-containingcleansing products, lipsticks, rouge, make-ups, care creams andsunscreen preparations.

[0105] Preference is given here to the use of a pyrimidinecarboxylicacid of the following formula II

[0106] in which R¹ is a radical H or C1-8-alkyl, R² is a radical H orC1-4-alkyl, and R³, R⁴, R⁵ and R⁶ are each, independently of oneanother, a radical from the group consisting of H, OH, NH₂ andC1-4-alkyl. Preference is given to the use of pyrimidinecarboxylic acidsin which R² is a methyl or ethyl group, and R¹ or R⁵ and R⁶ are H.Particular preference is given to the use of the pyrimidinecarboxylicacids ectoin ((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylicacid) and hydroxyectoin((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid). The formulations according to the invention preferably comprisepyrimidinecarboxylic acids of this type in amounts of up to 15% byweight. The pyrimidinecarboxylic acids are preferably employed here inratios of from 100:1 to 1:100 with respect to the compounds of theformula 1, with ratios in the range from 1:10 to 10:1 being particularlypreferred.

[0107] Of the aryl oximes, preference is given to the use of2-hydroxy-5-methyllaurophenone oxime, which is also known as HMLO, LPOor F5. Its suitability for use in cosmetic compositions is disclosed,for example, in DE-A-41 16 123. Preparations which comprise2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for thetreatment of skin diseases which are accompanied by inflammation. It isknown that preparations of this type can be used, for example, for thetherapy of psoriasis, various forms of eczema, irritative and toxicdermatitis, UV dermatitis and further allergic and/or inflammatorydiseases of the skin and integumentary appendages. Formulationsaccording to the invention which, in addition to the compound of theformula I, additionally comprise an aryl oxime, preferably2-hydroxy-5-methyllaurophenone oxime, exhibit surprisingantiinflammatory suitability. The formulations here preferably comprisefrom 0.01 to 10% by weight of the aryl oxime, it being particularlypreferred for the preparation to comprise from 0.05 to 5% by weight ofaryl oxime.

[0108] All compounds or components which can be used in the formulationsare either known or are commercially available or can be synthesised byknown processes.

[0109] The one or more compounds of the formula I can be incorporatedinto cosmetic formulations in the customary manner. Suitableformulations are those for external use, for example in the form of acream, lotion, gel or as a solution which can be sprayed onto the skin.Suitable for internal use are administration forms such as capsules,coated tablets, powders, tablet solutions or solutions.

[0110] Examples which may be mentioned of application forms of thecosmetic or pharmaceutical food supplement formulations according to theinvention are: solutions, suspensions, emulsions, PIT emulsions, pastes,ointments, gels, creams, lotions, powders, soaps, surfactant-containingcleansing preparations, oils, aerosols and sprays. Examples of otherapplication forms are sticks, shampoos and shower preparations. Anydesired customary excipients, auxiliaries and, if desired, furtheractive ingredients may be added to the formulation.

[0111] Preferred auxiliaries originate from the group consisting ofpreservatives, antioxidants, stabilisers, solubilisers, vitamins,colorants and odour improvers.

[0112] Ointments, pastes, creams and gels may comprise the customaryexcipients, for example animal and vegetable fats, waxes, paraffins,starch, tragacanth, cellulose derivatives, polyethylene glycols,silicones, bentonites, silica, talc and zinc oxide, or mixtures of thesesubstances.

[0113] Powders and sprays may comprise the customary excipients, forexample lactose, talc, silica, aluminium hydroxide, calcium silicate andpolyamide powder, or mixtures of these substances. Sprays mayadditionally comprise the customary propellants, for examplechlorofluorocarbons, propane/butane or dimethyl ether.

[0114] Solutions and emulsions may comprise the customary excipients,such as solvents, solubility promoters and emulsifiers, for examplewater, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, oils, inparticular cottonseed oil, peanut oil, wheatgerm oil, olive oil, castoroil and sesame oil, glycerol fatty acid esters, polyethylene glycols andfatty acid esters of sorbitan or mixtures of these substances.

[0115] Suspensions may comprise the customary excipients, such as liquiddiluents, for example water, ethanol or propylene glycol, suspendingagents, for example ethoxylated isostearyl alcohols, polyoxyethylenesorbitol esters and polyoxyethylene sorbitan esters, microcrystallinecellulose, aluminium metahydroxide, bentonite, agar agar and tragacanth,or mixtures of these substances.

[0116] Soaps may comprise the customary excipients, such as alkali metalsalts of fatty acids, salts of fatty acid monoesters, fatty acid proteinhydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils,plant extracts, glycerol, sugars, or mixtures of these substances.

[0117] Surfactant-containing cleansing products may comprise thecustomary excipients, such as salts of fatty alcohol sulfates, fattyalcohol ether sulfates, sulfosuccinic monoesters, fatty acid proteinhydrolysates, isothionates, imidazolinium derivatives, methyl taurates,sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fattyalcohols, fatty acid glycerides, fatty acid diethanolamides, vegetableand synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acidesters, or mixtures of these substances.

[0118] Face and body oils may comprise the customary excipients, such assynthetic oils, such as fatty acid esters, fatty alcohols, siliconeoils, natural oils, such as vegetable oils and oily plant extracts,paraffin oils or lanolin oils, or mixtures of these substances.

[0119] Further typical cosmetic application forms are also lipsticks,lipcare sticks, mascara, eyeliner, eyeshadow, rouge, powder make-up,emulsion make-up and wax make-up, and sunscreen, presun and aftersunpreparations.

[0120] The preferred preparation forms according to the inventioninclude, in particular, emulsions.

[0121] Emulsions according to the invention are advantageous andcomprise, for example, the said fats, oils, waxes and other fattysubstances, as well as water and an emulsifier, as usually used for aformulation of this type.

[0122] The lipid phase may advantageously be selected from the followinggroup of substances:

[0123] mineral oils, mineral waxes,

[0124] oils, such as triglycerides of capric or caprylic acid,furthermore natural oils, such as, for example, castor oil,

[0125] fats, waxes and other natural and synthetic fatty substances,preferably esters of fatty acids with alcohols having a low carbonnumber, for example with isopropanol, propylene glycol or glycerol, oresters of fatty alcohols with alkanoic acids having a low carbon numberor with fatty acids,

[0126] silicone oils, such as dimethylpolysiloxanes,diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

[0127] For the purposes of the present invention, the oil phase of theemulsions, oleogels or hydrodispersions or lipodispersions isadvantageously selected from the group consisting of esters of saturatedand/or unsaturated, branched and/or unbranched alkanecarboxylic acidshaving a chain length of from 3 to 30 carbon atoms and saturated and/orunsaturated, branched and/or unbranched alcohols having a chain lengthof from 3 to 30 carbon atoms, from the group consisting of esters ofaromatic carboxylic acids and saturated and/or unsaturated, branchedand/or unbranched alcohols having a chain length of from 3 to 30 carbonatoms. Ester oils of this type can then advantageously be selected fromthe group consisting of isopropyl myristate, isopropyl palmitate,isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate,n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecylstearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyloleate, erucyl erucate and synthetic, semi-synthetic and naturalmixtures of esters of this type, for example jojoba oil.

[0128] The oil phase may furthermore advantageously be selected from thegroup consisting of branched and unbranched hydrocarbons and waxes,silicone oils, dialkyl ethers, the group consisting of saturated orunsaturated, branched or unbranched alcohols, and fatty acidtriglycerides, specifically the triglycerol esters of saturated and/orunsaturated, branched and/or unbranched alkanecarboxylic acids having achain length of from 8 to 24, in particular 12-18, carbon atoms. Thefatty acid triglycerides may advantageously be selected, for example,from the group consisting of synthetic, semi-synthetic and natural oils,for example olive oil, sunflower oil, soya oil, peanut oil, rapeseedoil, almond oil, palm oil, coconut oil, palm kernel oil and the like.

[0129] Any desired mixtures of oil and wax components of this type mayalso advantageously be employed for the purposes of the presentinvention. It may also be advantageous to employ waxes, for examplecetyl palmitate, as the only lipid component of the oil phase.

[0130] The oil phase is advantageously selected from the groupconsisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecylisononanoate, isoeicosane, 2-ethylhexyl cocoate, C₁₂₋₁₅-alkyl benzoate,caprylic/capric acid triglyceride and dicapryl ether.

[0131] Particularly advantageous are mixtures of C₁₂₋₁₅-alkyl benzoateand 2-ethylhexyl isostearate, mixtures of C₁₂₋₁₅-alkyl benzoate andisotridecyl isononanoate, as well as mixtures of C₁₂₋₁₅-alkyl benzoate,2-ethylhexyl isostearate and isotridecyl isononanoate.

[0132] Of the hydrocarbons, paraffin oil, squalane and squalene mayadvantageously be used for the purposes of the present invention.

[0133] Furthermore, the oil phase may also advantageously have a contentof cyclic or linear silicone oils or consist entirely of oils of thistype, although it is preferred to use an additional content of otheroil-phase components in addition to the silicone oil or the siliconeoils.

[0134] The silicone oil to be used in accordance with the invention isadvantageously cyclomethicone (octamethylcyclotetrasiloxane). However,it is also advantageous for the purposes of the present invention to useother silicone oils, for example hexamethylcyclotrisiloxane,polydimethylsiloxane or poly(methylphenylsiloxane).

[0135] Also particularly advantageous are mixtures of cyclomethicone andisotridecyl isononanoate and of cyclomethicone and 2-ethylhexylisostearate.

[0136] The aqueous phase of the preparations according to the inventionoptionally advantageously comprises alcohols, diols or polyols having alow carbon number, and ethers thereof, preferably ethanol, isopropanol,propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethylor monobutyl ether, propylene glycol monomethyl, monoethyl or monobutylether, diethylene glycol monomethyl or monoethyl ether and analogousproducts, furthermore alcohols having a low carbon number, for exampleethanol, isopropanol, 1,2-propanediol or glycerol, and, in particular,one or more thickeners, which may advantageously be selected from thegroup consisting of silicon dioxide, aluminium silicates,polysaccharides or derivatives thereof, for example hyaluronic acid,xanthan gum, hydroxypropylmethylcellulose, particularly advantageouslyfrom the group consisting of the polyacrylates, preferably apolyacrylate from the group consisting of the so-called Carbopols, forexample Carbopol grades 980, 981, 1382, 2984 or 5984, in each caseindividually or in combination.

[0137] In particular, mixtures of the above-mentioned solvents are used.In the case of alcoholic solvents, water may be a further constituent.

[0138] Emulsions according to the invention are advantageous andcomprise, for example, the said fats, oils, waxes and other fattysubstances, as well as water and an emulsifier, as usually used for aformulation of this type.

[0139] In a preferred embodiment, the formulations according to theinvention comprise hydrophilic surfactants.

[0140] The hydrophilic surfactants are preferably selected from thegroup consisting of the alkyl glycosides, acyl lactylates, betaines andcoconut amphoacetates.

[0141] The alkyl glycosides are themselves advantageously selected fromthe group consisting of the alkyl glycosides that are distinguished bythe structural formula

[0142] where R is a branched or unbranched alkyl radical having from 4to 24 carbon atoms, and where {overscore (DP)} denotes a mean degree ofglycosidation of up to 2.

[0143] The value {overscore (DP)} represents the degree of glycosidationof the alkyl glycosides used in accordance with the invention and isdefined as$\overset{\_}{DP} = {{{\frac{p_{1}}{100} \cdot 1} + {\frac{p_{2}}{100} \cdot 2} + {\frac{p_{3}}{100} \cdot 3} + \ldots} = {\sum{\frac{p_{i}}{100} \cdot i}}}$

[0144] in which p₁, p₂, p₃. . . p_(i) represent the proportion of mono-,di-, tri- . . . i-glycosylated products in per cent by weight.Advantageous according to the invention are products having degrees ofglycosylation of 1-2, particularly advantageously of from 1.1 to 1.5,very particularly advantageously of 1.2-1.4, in particular of 1.3.

[0145] The value {overscore (DP)} takes into account the fact that alkylglycosides are generally, as a consequence of their preparation, in theform of mixtures of mono- and oligoglycosides. A relatively high contentof monoglycosides, typically in the order of 40-70% by weight, isadvantageous in accordance with the invention.

[0146] Alkyl glycosides which are particularly advantageously used forthe purposes of the present invention are selected from the groupconsisting of octyl glucopyranoside, nonyl glucopyranoside, decylglucopyranoside, undecyl glucopyranoside, dodecyl glucopyranoside,tetradecyl glucopyranoside and hexadecyl glucopyranoside.

[0147] It is likewise advantageous to employ natural or synthetic rawmaterials and auxiliaries or mixtures which are distinguished by aneffective content of the active ingredients used in accordance with theinvention, for example Plantaren® 1200 (Henkel KGaA), Oramix® NS 10(Seppic).

[0148] The acyl lactylates are themselves advantageously selected fromthe group consisting of the substances which are distinguished by thestructural formula

[0149] where R¹ is a branched or unbranched alkyl radical having from 1to 30 carbon atoms, and M⁺ is selected from the group consisting of thealkali metal ions and the group consisting of ammonium ions which aresubstituted by one or more alkyl and/or one or more hydroxyalkylradicals, or corresponds to half an equivalent of an alkaline earthmetal ion.

[0150] For example, sodium isostearyl lactylate, for example the productPathionic® ISL from the American Ingredients Company, is advantageous.

[0151] The betaines are advantageously selected from the groupconsisting of the substances which are distinguished by the structuralformula

[0152] where R² is a branched or unbranched alkyl radical having from 1to 30 carbon atoms.

[0153] R² is particularly advantageously a branched or unbranched alkylradical having from 6 to 12 carbon atoms.

[0154] For example, capramidopropylbetaine, for example the productTego® Betain 810 from Th. Goldschmidt AG, is advantageous.

[0155] A coconut amphoacetate which is advantageous for the purposes ofthe invention is, for example, sodium coconut amphoacetate, as availableunder the name Miranol® Ultra C32 from Miranol Chemical Corp.

[0156] The preparations according to the invention are advantageouslycharacterised in that the hydrophilic surfactant(s) is (are) present inconcentrations of 0.01-20% by weight, preferably 0.05-10% by weight,particularly preferably 0.1-5% by weight, in each case based on thetotal weight of the composition.

[0157] For use, the cosmetic and dermatological preparations accordingto the invention are applied to the skin and/or the hair in an adequateamount in the usual manner for cosmetics.

[0158] Cosmetic and dermatological preparations according to theinvention may exist in various forms. Thus, they may be, for example, asolution, a water-free preparation, an emulsion or microemulsion of thewater-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, forexample of the water-in-oil-in-water (W/O/W) type, a gel, a solid stick,an ointment or an aerosol. It is also advantageous to administer ectoinsin encapsulated form, for example in collagen matrices and otherconventional encapsulation materials, for example as celluloseencapsulations, in gelatine, wax matrices or liposomally encapsulated.In particular, wax matrices, as described in DE-A 43 08 282, have provenfavourable. Preference is given to emulsions. O/W emulsions areparticularly preferred. Emulsions, W/O emulsions and O/W emulsions areobtainable in a conventional manner.

[0159] Emulsifiers that can be used are, for example, the known W/O andO/W emulsifiers. It is advantageous to use further conventionalco-emulsifiers in the preferred O/W emulsions according to theinvention.

[0160] Co-emulsifiers which are advantageous according to the inventionare, for example, O/W emulsifiers, principally from the group consistingof the substances having HLB values of 11-16, very particularlyadvantageously having HLB values of 14.5-15.5, so long as the O/Wemulsifiers have saturated radicals R and R′. If the O/W emulsifiershave unsaturated radicals R and/or R′ or in the case of isoalkylderivatives, the preferred HLB value of such emulsifiers may also belower or higher.

[0161] It is advantageous to select the fatty alcohol ethoxylates fromthe group consisting of ethoxylated stearyl alcohols, cetyl alcohols,cetylstearyl alcohols (cetearyl alcohols). Particular preference isgiven to the following:

[0162] polyethylene glycol (13) stearyl ether (steareth-13),

[0163] polyethylene glycol (14) stearyl ether (steareth-14),

[0164] polyethylene glycol (15) stearyl ether (steareth-15),

[0165] polyethylene glycol (16) stearyl ether (steareth-16),

[0166] polyethylene glycol (17) stearyl ether (steareth-17),

[0167] polyethylene glycol (18) stearyl ether (steareth-18),

[0168] polyethylene glycol (19) stearyl ether (steareth-19),

[0169] polyethylene glycol (20) stearyl ether (steareth-20),

[0170] polyethylene glycol (12) isostearyl ether (isosteareth-12),

[0171] polyethylene glycol (13) isostearyl ether (isosteareth-13),

[0172] polyethylene glycol (14) isostearyl ether (isosteareth-14),

[0173] polyethylene glycol (15) isostearyl ether (isosteareth-15),

[0174] polyethylene glycol (16) isostearyl ether (isosteareth-16),

[0175] polyethylene glycol (17) isostearyl ether (isosteareth-17),

[0176] polyethylene glycol (18) isostearyl ether (isosteareth-18),

[0177] polyethylene glycol (19) isostearyl ether (isosteareth-19),

[0178] polyethylene glycol (20) isostearyl ether (isosteareth-20),

[0179] polyethylene glycol (13) cetyl ether (ceteth-13),

[0180] polyethylene glycol (14) cetyl ether (ceteth-14),

[0181] polyethylene glycol (15) cetyl ether (ceteth-15),

[0182] polyethylene glycol (16) cetyl ether (ceteth-16),

[0183] polyethylene glycol (17) cetyl ether (ceteth-17),

[0184] polyethylene glycol (18) cetyl ether (ceteth-18),

[0185] polyethylene glycol (19) cetyl ether (ceteth-19),

[0186] polyethylene glycol (20) cetyl ether (ceteth-20),

[0187] polyethylene glycol (13) isocetyl ether (isoceteth-13),

[0188] polyethylene glycol (14) isocetyl ether (isoceteth-14),

[0189] polyethylene glycol (15) isocetyl ether (isoceteth-15),

[0190] polyethylene glycol (16) isocetyl ether (isoceteth-16),

[0191] polyethylene glycol (17) isocetyl ether (isoceteth-17),

[0192] polyethylene glycol (18) isocetyl ether (isoceteth-18),

[0193] polyethylene glycol (19) isocetyl ether (isoceteth-19),

[0194] polyethylene glycol (20) isocetyl ether (isoceteth-20),

[0195] polyethylene glycol (12) oleyl ether (oleth-12),

[0196] polyethylene glycol (13) oleyl ether (oleth-13),

[0197] polyethylene glycol (14) oleyl ether (oleth-14),

[0198] polyethylene glycol (15) oleyl ether (oleth-15),

[0199] polyethylene glycol (12) lauryl ether (laureth-12),

[0200] polyethylene glycol (12) isolauryl ether (isolaureth-12),

[0201] polyethylene glycol (13) cetylstearyl ether (ceteareth-13),

[0202] polyethylene glycol (14) cetylstearyl ether (ceteareth-14),

[0203] polyethylene glycol (15) cetylstearyl ether (ceteareth-15),

[0204] polyethylene glycol (16) cetylstearyl ether (ceteareth-16),

[0205] polyethylene glycol (17) cetylstearyl ether (ceteareth-17),

[0206] polyethylene glycol (18) cetylstearyl ether (ceteareth-18),

[0207] polyethylene glycol (19) cetylstearyl ether (ceteareth-19),

[0208] polyethylene glycol (20) cetylstearyl ether (ceteareth-20).

[0209] It is furthermore advantageous to select the fatty acidethoxylates from the following group:

[0210] polyethylene glycol (20) stearate, polyethylene glycol (21)stearate, polyethylene glycol (22) stearate, polyethylene glycol (23)stearate, polyethylene glycol (24) stearate, polyethylene glycol (25)stearate, polyethylene glycol (12) isostearate, polyethylene glycol (13)isostearate, polyethylene glycol (14) isostearate, polyethylene glycol(15) isostearate, polyethylene glycol (16) isostearate, polyethyleneglycol (17) isostearate, polyethylene glycol (18) isostearate,polyethylene glycol (19) isostearate, polyethylene glycol (20)isostearate, polyethylene glycol (21) isostearate, polyethylene glycol(22) isostearate, polyethylene glycol (23) isostearate, polyethyleneglycol (24) isostearate, polyethylene glycol (25) isostearate,polyethylene glycol (12) oleate, polyethylene glycol (13) oleate,polyethylene glycol (14) oleate, polyethylene glycol (15) oleate,polyethylene glycol (16) oleate, polyethylene glycol (17) oleate,polyethylene glycol (18) oleate, polyethylene glycol (19) oleate,polyethylene glycol (20) oleate.

[0211] An ethoxylated alkyl ether carboxylic acid or salt thereof whichcan advantageously be used is sodium laureth-11 carboxylate. An alkylether sulfate which can advantageously be used is sodium laureth-14sulfate. An ethoxylated cholesterol derivative which can advantageouslybe used is polyethylene glycol (30) cholesteryl ether. Polyethyleneglycol (25) soyasterol has also proven successful. Ethoxylatedtriglycerides which can advantageously be used are the polyethyleneglycol (60) evening primrose glycerides.

[0212] It is furthermore advantageous to select the polyethylene glycolglycerol fatty acid esters from the group consisting of polyethyleneglycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate,polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23)glyceryl laurate, polyethylene glycol (6) glyceryl caprate/caprinate,polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20)glyceryl isostearate, polyethylene glycol (18) glyceryl oleate/cocoate.

[0213] It is likewise favourable to select the sorbitan esters from thegroup consisting of polyethylene glycol (20) sorbitan monolaurate,polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20)sorbitan monoisostearate, polyethylene glycol (20) sorbitanmonopalmitate, polyethylene glycol (20) sorbitan monooleate.

[0214] Optional W/O emulsifiers, but ones which may nevertheless beadvantageous for the purposes of the invention are the following:

[0215] fatty alcohols having from 8 to 30 carbon atoms, monoglycerolesters of saturated and/or unsaturated, branched and/or unbranchedalkanecarboxylic acids having a chain length of from 8 to 24 carbonatoms, in particular 12-18 carbon atoms, diglycerol esters of saturatedand/or unsaturated, branched and/or unbranched alkanecarboxylic acidshaving a chain length of from 8 to 24 carbon atoms, in particular 12-18carbon atoms, monoglycerol ethers of saturated and/or unsaturated,branched and/or unbranched alcohols having a chain length of from 8 to24 carbon atoms, in particular 12-18 carbon atoms, diglycerol ethers ofsaturated and/or unsaturated, branched and/or unbranched alcohols havinga chain length of from 8 to 24 carbon atoms, in particular 12-18 carbonatoms, propylene glycol esters of saturated and/or unsaturated, branchedand/or unbranched alkanecarboxylic acids having a chain length of from 8to 24 carbon atoms, in particular 12-18 carbon atoms, and sorbitanesters of saturated and/or unsaturated, branched and/or unbranchedalkanecarboxylic acids having a chain length of from 8 to 24 carbonatoms, in particular 12-18 carbon atoms.

[0216] Particularly advantageous W/O emulsifiers are glycerylmonostearate, glyceryl monoisostearate, glyceryl monomyristate, glycerylmonooleate, diglyceryl monostearate, diglyceryl monoisostearate,propylene glycol monostearate, propylene glycol monoisostearate,propylene glycol monocaprylate, propylene glycol monolaurate, sorbitanmonoisostearate, sorbitan monolaurate, sorbitan monocaprylate, sorbitanmonoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol,arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachylalcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether(steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glycerylmonocaprylate.

[0217] The preparation according to the invention is particularlysuitable for protecting human skin against ageing processes and againstoxidative stress, i.e. against damage caused by free radicals, as areproduced, for example, by solar irradiation, heat or other influences.In this connection, it is in the various administration forms usuallyused for this application. For example, it may, in particular, be in theform of a lotion or emulsion, such as in the form of a cream or milk(O/W, W/O, O/W/O, W/O/W), in the form of oily-alcoholic, oily-aqueous oraqueous-alcoholic gels or solutions, in the form of solid sticks or maybe formulated as an aerosol.

[0218] The formulation may comprise cosmetic adjuvants which are usuallyused in this type of preparation, such as, for example, thickeners,softeners, moisturisers, surface-active agents, emulsifiers,preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyesand/or pigments which colour the composition itself or the skin, andother ingredients usually used in cosmetics.

[0219] The dispersant or solubiliser used can be an oil, wax or otherfatty substance, a lower monoalcohol or lower polyol or mixturesthereof. Particularly preferred monoalcohols or polyols include ethanol,isopropanol, propylene glycol, glycerol and sorbitol.

[0220] A preferred embodiment of the invention is an emulsion in theform of a protective cream or milk which, apart from the compound(s) ofthe formula I, comprises, for example, fatty alcohols, fatty acids,fatty acid esters, in particular triglycerides of fatty acids, lanolin,natural and synthetic oils or waxes and emulsifiers in the presence ofwater.

[0221] Further preferred embodiments are oily lotions based on naturalor synthetic oils and waxes, lanolin, fatty acid esters, in particulartriglycerides of fatty acids, or oily-alcoholic lotions based on a loweralcohol, such as ethanol, or a glycerol, such as propylene glycol,and/or a polyol, such as glycerol, and oils, waxes and fatty acidesters, such as triglycerides of fatty acids.

[0222] The cosmetic preparation according to the invention may also bein the form of an alcoholic gel which comprises one or more loweralcohols or polyols, such as ethanol, propylene glycol or glycerol, anda thickener, such as siliceous earth. The oily-alcoholic gels alsocomprise natural or synthetic oil or wax.

[0223] The solid sticks consist of natural or synthetic waxes and oils,fatty alcohols, fatty acids, fatty acid esters, lanolin and other fattysubstances.

[0224] If a preparation is formulated as an aerosol, the customarypropellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, areusually used.

[0225] The cosmetic formulation may also be used to protect the hairagainst photochemical damage in order to prevent colour changes,bleaching or damage of a mechanical nature. In this case, a suitableformulation is in the form of a rinse-out shampoo, lotion, gel oremulsion, the formulation in question being applied before or aftershampooing, before or after colouring or bleaching or before or afterpermanent waving. It is also possible to select a formulation in theform of a lotion or gel for styling or treating the hair, in the form ofa lotion or gel for brushing or blow-waving, in the form of a hairlacquer, permanent waving composition, colorant or bleach for the hair.Apart from the compound of the formula 1, the cosmetic or pharmaceuticalformulation may comprise various adjuvants used in this type ofcomposition, such as surfactants, thickeners, polymers, softeners,preservatives, foam stabilisers, electrolytes, organic solvents,silicone derivatives, oils, waxes, antigrease agents, dyes and/orpigments which colour the composition itself or the hair, or otheringredients usually used for hair care.

[0226] The cosmetic preparations according to the invention can beprepared using techniques which are well known to the person skilled inthe art.

[0227] To protect the skin and/or natural or sensitised hair againstsunlight, a cosmetic preparation comprising one or more compounds of theformula I is applied to the skin or the hair. Sensitised hair here istaken to mean hair which has been subjected to a chemical treatment,such as a permanent waving treatment, a colouring process or bleachingprocess.

[0228] Furthermore, it has also been noted that compounds of the formulaI can have a stabilising effect on the formulation. When used incorresponding products, the latter are thus also stable for longer anddo not change their appearance. In particular, the effectiveness of theingredients, for example vitamins, is retained even in the case ofapplication over extended periods or extended storage. This isparticularly advantageous in the case of compositions for protecting theskin against the effect of UV rays since these cosmetics are exposed toparticularly high stresses by UV radiation. In a2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, it was found that4,6,3′,4′-tetrahydroxybenzylcoumaranone has better free-radicalscavenger properties than tocopherol (vitamin E). The performance of theDPPH assay is described in Brand-Williams, W., Cuvelier, M. E. & Berset,C. “Use of a free radical method to evaluate antioxidant activity”; FoodScience & Technology28, 25-30 (1995). Gamez, E. J. et al. “Antioxidantflavonoid glycosides from Daphniphyllum calycinum”; J. Nat. Prod. 61,706-708 (1998); Ancerewicz, J. et al. “Structure-property relationshipsof trimetazidine derivatives and model compounds as potentialantioxidants”; Free Radic. Biol. Med. 25,113-120 (1998).

[0229] 2,2-Diphenyl-1-picrylhydrazyl is a free radical which is stablein solution. The unpaired electron results in a strong absorption bandat 515 nm, and the solution has a dark violet colour. In the presence ofa free-radical scavenger, the electron is paired, the absorptiondisappears, and the decoloration proceeds stoichiometrically taking intoaccount the electrons taken up. The absorbance is measured in aphotometer. The anti-free-radical property of the substance to be testedis determined by measuring the concentration at which 50% of the2,2-diphenyl-1-picrylhydrazyl employed has reacted with the free-radicalscavenger. This concentration is expressed as EC₅₀, a value which can beconsidered to be a property of the substance under the given measurementconditions. The substance investigated is compared with a standard (forexample tocopherol).

[0230] The evaluation is carried out graphically by plotting the testsubstance/-DPPH molar ratio against the percentage decrease inabsorbance, and the EC₅₀ is determined by reading off at 50%. Inaddition, the slope of the straight lines in the linear region isdetermined and the EC₅₀ calculated.

[0231] The positive effects of compounds of the formula I give rise totheir particular suitability for use in cosmetic or pharmaceuticalformulations.

[0232] The properties of compounds of the formula I should likewise beregarded as positive for use in foods or as food supplements or asfunctional foods. The further explanations given for foods also applycorrespondingly to food supplements and functional foods.

[0233] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention include all materialswhich are suitable for consumption by animals or consumption by humans,for example vitamins and provitamins thereof, fats, minerals or aminoacids. (The foods may be solid, but also liquid, i.e. in the form of abeverage). Foods which can be enriched with one or more compounds of theformula I in accordance with the present invention are, for example,also foods which originate from a single natural source, such as, forexample, sugar, unsweetened juice, squash or puree of a single plantspecies, such as, for example, unsweetened apple juice (for example alsoa mixture of different types of apple juice), grapefruit juice, orangejuice, apple compote, apricot squash, tomato juice, tomato sauce, tomatopuree, etc. Further examples of foods which can be enriched with one ormore compounds of the formula I in accordance with the present inventionare corn or cereals from a single plant species and materials producedfrom plant species of this type, such as, for example, cereal syrup, ryeflour, wheat flour or oatbran. Mixtures of foods of this type are alsosuitable for being enriched with one or more compounds of the formula Iin accordance with the present invention, for example multivitaminpreparations, mineral mixtures or sweetened juice. As further examplesof foods which can be enriched with one or more compounds of the formulaI in accordance with the present invention, mention may be made of foodpreparations, for example prepared cereals, biscuits, mixed drinks,foods prepared especially for children, such as yoghurt, diet foods,low-calorie foods or animal feeds.

[0234] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention thus include alledible combinations of carbohydrates, lipids, proteins, inorganicelements, trace elements, vitamins, water or active metabolites ofplants and animals.

[0235] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention are preferablyadministered orally, for example in the form of meals, pills, tablets,capsules, powders, syrup, solutions or suspensions.

[0236] The foods according to the invention enriched with one or morecompounds of the formula I can be prepared using techniques which arewell known to the person skilled in the art.

[0237] Due to their action as antioxidants or free-radical scavengers,compounds of the formula I containing radicals as defined above, where—X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—, —CH(NR⁵R⁶)— or—CH(OR⁵)—, are also suitable as medicaments. In this case, they supportor replace natural mechanisms which scavenge free radicals in the body.The compounds of the formula I can in some cases be compared in terms oftheir action with free-radical scavengers such as vitamin C. Compoundsof the formula I can be used, for example, for preventative treatment ofinflammation and allergies of the skin and in certain cases forpreventing certain types of cancer.

[0238] Compounds of the formula I in which —X— is ═CH— and at least oneradical from R¹, R², R³ and R⁴ is a group selected from the followinglist:

[0239] straight-chain or branched C₁- to C₁₂-alkylcarbonyl groups,

[0240] straight-chain or branched C₃- to C₁₂-alkenylcarbonyl groups,

[0241] straight-chain or branched C₁- to C₁₂-hydroxyalkyl groups, inwhich the hydroxyl group may be bonded to a primary or secondary carbonatom of the chain, and furthermore the alkyl chain may also beinterrupted by oxygen,

[0242] C₃- to C₁₀-cycloalkylcarbonyl groups and C₃- to C₁₂-cycloalkenyland/or cycloalkenylcarbonyl groups, in which each of the rings may alsobe bridged by —(CH₂)_(n)— groups, where n=from 1 to 3,

[0243] aryl and/or arylcarbonyl groups,

[0244] heteroaryl and/or heteroarylcarbonyl groups, where these groupsmay be substituted by alkyl, hydroxyl, alkoxy, amino, mono- anddi-alkylamino, sulfonic acid, carboxyl and/or halogen groups,

[0245] mono- and/or oligoglycosyl radicals,

[0246] in which Me is a proton or an alkali metal ion, in particular asodium or potassium ion, are also suitable as medicaments owing to theabove-mentioned properties.

[0247] Compounds of the formula I are particularly suitable for thepreparation of a medicament for the treatment of inflammation, allergiesand irritation, in particular of the skin.

[0248] It is furthermore possible to prepare medicaments which act as avein tonic, as an agent for increasing the strength of bloodcapillaries, as cuperose inhibitor, as chemical, physical or actinicerythema inhibitor, as agent for the treatment of sensitive skin, asdecongestant, as desiccant, as slimming agent, as anti-wrinkle agent, asstimulator for the synthesis of components of the extracellular matrix,as strengthening agent for improving skin elasticity, and as anti-ageingagent.

[0249] Furthermore, compounds of the formula I exhibit antiallergic andanti-inflammatory and antiirritative actions. They are thereforesuitable for the preparation of medicaments for the treatment ofinflammation or allergic reactions.

[0250] The invention furthermore relates to compounds of the formula I

[0251] in which the variables are as defined above, which arecharacterised in that at least one radical from R¹, R², R³ and R⁴ is notH.

[0252] Through the radicals R¹, R², R³ and R⁴, the properties of thecompounds can be matched virtually as desired to the respective needs.Thus, the introduction of, for example, alkyl chains enables thesolubility of the compounds in oils to be improved. The introduction ofUV-absorbent groups enables the preparation of compounds which are bothantioxidants or free-radical scavengers and UV absorbers. The radicalscan be introduced, for example, starting from the known compounds4,6,3′,4′-tetra-hydroxybenzylcoumaran-3-one (X═—CH₂—) or4,6,3′,4′-tetrahydroxyaurone (X══CH—) by processes known per se to theperson skilled in the art. Thus, alkyl chains can be introduced byreaction of the parent compounds with the corresponding alkyl halides inthe presence of a strong base in a suitable solvent, for exampledimethylformamide. If the radicals R¹ to R⁴ form an ester bond, this canbe carried out, for example, by reaction with a corresponding acidchloride. General preparation processes are described, for example, inHouben-Weyl; Georg Thieme Verlag, Stuttgart. Some suitable reactions arementioned below as representative:

[0253] Linking by ester formation: Houben-Weyl; Volume VIII, pp. 503ff.; editor: E. Müller, Houben-Weyl; Volume E5, pp. 656 ff.; editor: J.Falbe. Linking by ether formation: Houben-Weyl; Volume VI/3, pp. 1 ff.;editor: E. Müller.

[0254] Linking by sulfonic acid ester: Houben-Weyl; Volume IX; pp. 659ff.; editor: E. Müller.

[0255] Some precursors of the radicals R which are suitable forintroduction of the radicals into the parent compounds are indicated inscheme 1 as representative. This list is only illustrative and showsonly a small selection from the range of possible precursors. It isreadily possible for the person skilled in the art to provide othersuitable leaving groups, for example a tosylate group or a triflategroup, instead of the halides. For example, introduction of the radicalsvia an ester function is also possible through correspondingtransesterification reactions.

[0256] Y here is a suitable leaving group.

[0257] The compounds may either be in the form of pure compounds, i.e.,for example, only certain radicals are formed by the groups indicatedabove, while the other radicals are hydrogen. However, it is alsopossible for the radicals to be randomly distributed, i.e., for example,in the form of an isomer mixture or a mixture of compounds in which 1,2, 3 or 4 hydrogen atoms of the parent compound have been replaced byone or more of the radicals indicated above.

[0258] The preferred compounds according to the invention include thecompounds in which at least one radical from R¹, R², R³ and R⁴is an—SO₃Me or —PO₃Me₂ group. These compounds have improved water solubilitycompared with the hydroxyl compounds and can therefore be incorporatedreadily into water-containing formulations. Particular preference isgiven here to the sulfates, in particular the trisulfates of the formulaIII

[0259] which may be in pure form or in the form of a mixture with thecorresponding mono- and disulfates. Particular preference is given tothe sulfate, in particular the trisulfate, of4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one

[0260] which is preferably employed in the form of a soluble salt,preferably an alkali metal salt, and is either in pure form, or, in afurther preferred embodiment, in the form of a mixture with the mono-and disulfate.

[0261] For the purposes of the invention, particular preference is givento compounds of the formula I in which —X— is a single bond, —CH₂—,—C(O)—, ═C(OR⁵)—, —C(NR⁵)—, —CH(NR⁵R⁶)— or —CH(OR⁵)—.

[0262] A reaction of the parent compound with the corresponding reactiveprecursors of the radicals R¹ to R⁴ is carried out by processes known tothe person skilled in the art and in the usual solvents. Suitablesolvents are, for example, chlorinated hydrocarbons, dimethyl sulfoxide,dimethylformamide, etc.

[0263] The present invention furthermore relates to the use of apreferred compound of the formula I according to the invention in which—X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—, —CH(NR⁵R⁶)— or—CH(OR⁵)—, and the other variables have the general meaning given above,as an antioxidant, in particular for cosmetic formulations or foods.

[0264] The invention furthermore relates to the stabilisation of UVfilters. A known and effective class of light-protection filtersubstances is formed by dibenzoylmethane derivatives. However, it isdisadvantageous that these substances are very easily decomposed by UVlight, and their protective properties are thus lost. An example of alight-protection filter from this class of compounds which is availableon the market is 4-(tert-butyl)-4′-methoxydibenzoylmethane, which hasthe following structure:

[0265] Surprisingly, it has now been found that compounds of the formulaI in which —X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—,—CH(NR⁵R⁶)— or —CH(OR⁵)— have a very good stabilisation action fordibenzoylmethanes, in particular 4-(tert-butyl)-4-methoxybenzoylmethane.A particularly high stabilisation action has been found for a compoundof the formula I in which X ═—CH₂— and R¹═R²═R³═R⁴═H. By incorporatingmixtures of these compounds into cosmetics, it is now possible toprepare light stabilisers using dibenzoylmethanes which exhibit only aslight reduction in the protective action against UV rays, or none atall, even on extended exposure to the sun, for example during sunbathingfor a number of hours.

[0266] The invention is explained in greater detail by means of examplesand with reference to a drawing.

[0267] In the formulations listed below, “sulfated coumaranone,potassium salt” or THBC sulfate is taken to mean a mixture of the mono-,di- and trisulfates of 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one inwhich the compounds in the mixture are in the form of the potassiumsalt.

[0268] Antaron® V-220 is marketed by GAF, Frechen, Del.

[0269] Carbomer Ultrez-10 is sold by Goodrich, Neuss, Del.

[0270] Dehymuls® E is a mixture of dicocoyl pentaerythrityl citrate,sorbitol sesquioleate, beeswax and aluminium stearate and is marketed byHenkel KGaA, Düsseldorf, DE.

[0271] Eusolex® 2292, Eusolex® HMS, Eusolex® 6300 and Eusolex® 232 areUV filters which are marketed by Merck KGaA, Darmstadt.

[0272] HMLO stands for 5-hydroxy-5-methyllaurophenone oxime.

[0273] Luvitol® EHO is marketed by BASF AG, Ludwigshafen, DE.

[0274] MBTTBP is2,2′-methylenebis(6-2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol.

[0275] Pemulen® TR-1 is an acrylate/C₁₀-C₃₀-alkyl acrylate polymer whichis marketed by Goodrich, Neuss, DE.

[0276] Pemulen® TR-2 is an acrylate/C₁₀-C₃₀-alkyl acrylate polymer whichis marketed by Goodrich, Neuss.

[0277] Performa® V825 is a synthetic wax which is marketed by New Phase,NJ08554.

[0278] Oxynex® K is a mixture of PEG-8, tocopherol, ascorbyl palmitate,ascorbic acid and citric acid and is marketed by Merck KGaA, Darmstadt.

[0279] Uvasorb® HEB is a dioctylbutamidotriazone and is marketed by 3VSigma.

EXAMPLE 1

[0280] Care lotion (W/O) for application to the skin % by wt. A4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 1.00 Polyglyceryl2-dipolyhydroxystearate 5.00 Beeswax 0.50 Zinc stearate 0.50 Hexyllaurate 9.00 Cetyl isononanoate 6.00 Shea butter 0.50 DL-α-Tocopherolacetate 1.00 B Glycerol 5.00 Magnesium sulfate heptahydrate 1.00Preservatives q.s. Water, demineralised aqua to 100.00

Preparation

[0281] Phase A is warmed to 75° C. and phase B to 80° C. Phase B isslowly added to phase A with stirring. After homogenisation, the mixtureis cooled with stirring. Perfumes are added at a temperature of 40° C.

[0282] The preservatives used are the following:

[0283] 0.05% of propyl 4-hydroxybenzoate

[0284] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 2

[0285] Care lotion (W/O) for application to the skin % by wt. APolyglyceryl 2-dipolyhydroxystearate 5.00 Beeswax 0.50 Zinc stearate0.50 Hexyl laurate 9.00 Cetyl isononanoate 6.00 Shea butter 0.50DL-α-Tocopherol acetate 1.00 B Sulfated coumaranone, potassium salt 0.50Glycerol 5.00 Magnesium sulfate heptahydrate 1.00 Preservative q.s.Water, demineralised to 100.00

Preparation

[0286] Phase A is warmed to 75° C. and phase B to 80° C. Phase B isslowly added to phase A with stirring. After homogenisation, the mixtureis cooled with stirring. Perfumes are added at a temperature of 40° C.

[0287] The preservatives used are the following:

[0288] 0.05% of propyl 4-hydroxybenzoate

[0289] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 3

[0290] Skin cream (O/W) % by wt. A Paraffin 2.00 Isohexadecane 2.00Isopropyl palmitate 3.00 Soya oil 0.50 Dimethicone 1.00 Cetyl alcohol1.00 Sorbitol stearate 1.50 Cetyl alcohol (and) cetyl glycoside 4.00(-)-α-Bisabolol 0.30 B Water, demineralised to 100.00 Sulfatedcoumaranone, potassium salt 0.20 Glycerol, 87% 10.00  D-Panthenol 0.50D-(+)-Biotin 0.05 Preservatives q.s. C Xanthan gum 0.30 D Perfume 0.20

Preparation

[0291] Phase A and phase B are warmed separately to 75° C. Phase C isthen slowly added to phase B and stirred until the mixture ishomogenised. The resultant mixture B/C is added to phase A at atemperature of 75° C., and the mixture is homogenised. After cooling to35° C., perfumes are added.

[0292] The preservatives used are 0.05% of propyl 4-hydroxybenzoate,0.15% of methyl 4-hydroxybenzoate and 0.30% of Germall 115 (ISP,Frechen).

EXAMPLE 4

[0293] A 4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 0.10 Paraffin 2.00Isohexadecane 2.00 Isopropyl palmitate 3.00 Soya oil 0.50 Dimethicone1.00 Cetyl alcohol 1.00 Sorbitol stearate 1.50 Cetyl alcohol (and) cetylglycoside 4.00 (-)-α-Bisabolol 0.30 B Water, demineralised to 100.00Glycerol, 87% 10.00  D-Panthenol 0.50 D-(+)-Biotin 0.05 Preservativesq.s. C Xanthan gum 0.30 D Perfume 0.20

Preparation

[0294] Phase A and phase B are warmed separately to 75° C. Phase C isthen slowly added to phase B and stirred until the mixture ishomogenised. The resultant mixture B/C is added to phase A at atemperature of 75° C., and the mixture is homogenised. After cooling to35° C., perfumes are added.

[0295] The preservatives used are the following:

[0296] 0.05% of propyl 4-hydroxybenzoate

[0297] 0.15% of methyl 4-hydroxybenzoate

[0298] 0.30% of Germall 115 (ISP, Frechen).

EXAMPLE 5

[0299] Sunscreen spray (O/W) % by wt. A4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 0.50 Eusolex ® 2292 (Art. No.105382) 7.50 Eusolex ® HMS (Art. No. 111412) 7.00 Steareth-2 0.40Steareth-10 0.80 Pemulen ® TR-2 0.18 Propylene glycol isoceteth-3acetate 5.00 Performa ® V 825 0.80 Dimethicone 1.00 Oxynex ® K (Art. No.108324) 0.10 B Eusolex ® 232 (Art. No. 105372) 1.00 Triethanolamine 0.90Propane-1,2-diol 2.00 Preservative 0.50 Water, demineralised to 100.00

Preparation Phase B

[0300] The water is mixed with the triethanolamine, and Eusolex® 232 issubsequently added with stirring. As soon as everything has dissolved,the further constituents of phase B are added and the mixture issubsequently warmed to 80° C.

Phase A

[0301] The constituents of phase A with the exception of Pemulen® TR-2are combined and warmed to 80° C. The Pemulen® TR-2 is subsequentlyadded with stirring.

[0302] Preparation of the sunscreen:

[0303] Phase B is slowly added to phase A with stirring. Afterhomogenisation, the mixture is cooled with stirring.

[0304] The preservatives used are the following:

[0305] 0.05% of propyl 4-hydroxybenzoate

[0306] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 6

[0307] Sunscreen spray (01W) % by wt. A Eusolex ® 2292 (Art. No. 105382)7.50 Eusolex ® HMS (Art. No. 111412) 7.00 Steareth-2 0.40 Steareth-100.80 Pemulen ® TR-2 0.18 Propylene glycol isoceteth-3 acetate 5.00Performa ® V 825 0.80 Dimethicone 1.00 Oxynex ® K (Art. No. 108324) 0.10B Sulfated coumaranone, potassium salt 0.20 Eusolex ® 232 (Art. No.105372) 1.00 Triethanolamine 0.90 Propane-1,2-diol 2.00 Water,demineralised aqua to 100.00

Preparation Phase B

[0308] The water is mixed with the triethanolamine, and Eusolex® 232 issubsequently added with stirring. As soon as everything has dissolved,the further constituents of phase B are added and the mixture issubsequently warmed to 80° C.

Phase A

[0309] The constituents of phase A with the exception of Pemulen® TR-2are combined and warmed to 80° C. The Pemulen® TR-2 is subsequentlyadded with stirring.

[0310] Preparation of the sunscreen:

[0311] Phase B is slowly added to phase A with stirring. Afterhomogenisation, the mixture is cooled with stirring.

[0312] The preservatives used are the following:

[0313] 0.05% of propyl 4-hydroxybenzoate

[0314] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 7

[0315] Sunscreen gel (aqueous) % by wt. A4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 0.10 Eusolex ® 232 (Art. No.105372) 4.00 Sodium hydroxide solution 6.00 Glycerol 3.00Propane-1,2-diol 2.00 Preservatives q.s. Water, demineralised to 100.00B Carbomer Ultrez-10 0.70 Water, demineralised 60.00  C Sodium hydroxidesolution (10%) 1.50 Water, demineralised 4.00

Preparation

[0316] Carbomer Ultrez-10 is completely dispersed in the water of phaseB. Phase C is subsequently added slowly, and the mixture is homogenised.For phase A, firstly the water is added to the sodium hydroxide solutionand then the Eusolex® 232 is added and completely dissolved withstirring. When a clear solution has been obtained, the furtherconstituents of phase A are added. Phase A is subsequently added inportions to the mixture of phases B and C, with homogenisation aftereach addition.

[0317] The preservative used is the following:

[0318] 0.20% of methyl 4-hydroxybenzoate

EXAMPLE 8

[0319] Sunscreen gel (O/W) % by wt. A4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 0.10 Eusolex ® 6300 (Art. No.5385) 0.75 Luvitol ® EHO 10.00  Dimethicone 2.00 Shea butter 5.00Antaron ® V-220 2.00 Oxynex ® K 1.00 B Eusolex ® 232 (Art. No. 5372)0.75 Tris(hydroxymethyl)aminomethane 0.33 Preservatives q.s. Water,demineralised 20.00  C Tris(hydroxymethyl)aminomethane 1.20 Water,demineralised 10.00  D Pemulen ® TR-1 0.60 Water, demineralised to100.00

Preparation

[0320] The Pemulen® TR-1 is dissolved in the water of phase D. Thetris(hydroxymethyl)aminomethane is dissolved in the water of phase C,and the solution is added to phase D. Thetris(hydroxymethyl)aminomethane is dissolved in the water of phase B,and the Eusolex® 232 is then added with stirring. When a clear solutionhas been obtained, the further constituents of phase B are added, andphase B is then added to the mixture of phases C and D, and the mixtureis homogenised. The constituents of phase A are combined and warmed.Phase A is then added to the mixture of the remaining phases withhomogenisation.

[0321] The preservatives used are the following:

[0322] 0.05% of propyl 4-hydroxybenzoate

[0323] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 9

[0324] Sunscreen gel (O/W) % by wt. A Eusolex ® 6300 (Art. No. 5385)0.75 Luvitol ® EHO 10.00  Dimethicone 2.00 Shea butter 5.00 Antaron ®V-220 2.00 Oxynex ® K liquid (Arty. No. 8324) 1.00 B Sulfatedcoumaranone, potassium salt 1.00 Eusolex ® 232 (Art. No. 5372) 0.75Tris(hydroxymethyl)aminomethane 0.33 Preservatives q.s. Water,demineralised 20.00  C Tris(hydroxymethyl)aminomethane 1.20 Water,demineralised 10.00  D Pemulen ® TR-1 0.60 Water, demineralised to100.00

Preparation

[0325] The Pemulen® TR-1 is dissolved in the water of phase D. Thetris(hydroxymethyl)aminomethane is dissolved in the water of phase C,and the solution is added to phase D. Thetris(hydroxymethyl)aminomethane is dissolved in the water of phase B,and the Eusolex® 232 is then added with stirring. When a clear solutionhas been obtained, the further constituents of phase B are added, andphase B is then added to the mixture of phases C and D, and the mixtureis homogenised. The constituents of phase A are combined and warmed.Phase A is then added to the mixture of the remaining phases withhomogenisation.

[0326] The preservatives used are the following: 0.05% of propyl4-hydroxybenzoate and 0.15% of methyl 4-hydroxybenzoate.

EXAMPLE 10

[0327] Sunscreen lotion (W/O) with UVA/B protection % by wt. A4,6,3′,4′-Tetrahydroxybenzylcoumaran-3-one 0.05 Eusolex ® 2292 (Art. No.1.05382) 3.00 Eusolex ® 4360 (Art. No. 1.05376) 2.00 Dehymuls ® E 6.00Hardened castor oil 1.00 Beeswax 2.00 Oleyl erucate 6.00 Decyl oleate6.00 Dicapryl ether 5.00 Dimethicone 1.00 B Glycerol (87%) 5.00Magnesium sulfate heptahydrate 1.00 Preservatives q.s. Water,demineralised to 100.00

Preparation

[0328] The constituents of phases A and B are combined separately. PhaseA is warmed to 75° C. and phase B separately to 80° C. Phase B is addedto phase A with homogenisation. The mixture is subsequently cooled withstirring.

[0329] The preservatives used are the following:

[0330] 0.05% of propyl 4-hydroxybenzoate

[0331] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 11

[0332] Sunscreen lotion (W/O) with UVA/B protection % by wt. A Eusolex ®2292 (Art. No. 1.05382) 3.00 Eusolex ® 4360 (Art. No. 1.05376) 2.00Dehymuls ® E 6.00 Hardened castor oil 1.00 Beeswax 2.00 Oleyl erucate6.00 Decyl oleate 6.00 Dicapryl ether 5.00 Dimethicone 1.00 B Sulfatedcoumaranone, potassium salt 0.50 Glycerol (87%) 5.00 Magnesium sulfateheptahydrate 1.00 Preservatives q.s. Water, demineralised to 100.00

Preparation

[0333] The constituents of phases A and B are combined separately. PhaseA is warmed to 75° C. and phase B separately to 80° C. Phase B is addedto phase A with homogenisation. The mixture is subsequently cooled withstirring.

[0334] The preservatives used are the following:

[0335] 0.05% of propyl 4-hydroxybenzoate

[0336] 0.15% of methyl 4-hydroxybenzoate

EXAMPLE 12 Preparation of 4,6,3′,4′-tetrahydroxycoumaran-3-one

[0337] 10 g of quercetin are introduced in portions into 11 of boilingwater. 85 g of sodium carbonate and 200 g of sodium dithionite aresubsequently added, and the suspension is stirred at 100° C. for 25minutes. The mixture is then cooled to 5° C., and 130 ml of fuminghydrochloric acid (37%) are slowly added dropwise. The mixture isstirred at low temperature for a further 2 hours and subsequentlyfiltered. The 2.6 g residue consists of4,6,3′,4′-tetrahydroxycoumaranone which is still contaminated withquercetin.

[0338] The filtrate is extracted firstly with 700 ml and subsequentlywith 200 ml of ethyl acetate. The combined organic phases are washedwith water (200 ml), saturated NaCl solution (200 ml) and dried oversodium sulfate. After filtration, the solvent is distilled off underreduced pressure, giving a yellow solid (4.53 g).

EXAMPLE 13 Preparation of Sulfated4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one

[0339] 23.8 g of tetrabutylammonium hydrogensulfate and 21.7 g ofN,N′-dicyclohexylcarbodiimide were dissolved in 250 ml of dry pyridine.10 g of 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one were then added, andthe mixture was stirred at 50° C. overnight. After cooling to roomtemperature, the mixture was filtered, and 250 ml of methanol were addedto the filtrate. After the mixture had been left to stand overnight, theprecipitate was again filtered off, the filtrate was evaporated to 150ml under reduced pressure, and the precipitate was again filtered off. Asolution of 1.5 g of potassium carbonate in 250 ml of methanol was addedto the filtrate. After 5 ml of water had been added to the mixture, themixture was transferred into two centrifuge tubes and centrifuged. Theliquid phase was decanted off, and the solid residue was dried in avacuum drying cabinet.

[0340] Yield: 2.23 g of pale-brown powder, mixture of tri-, di- andmonosulfate.

EXAMPLE 14 Determination of the EC₅₀ of4,6,3′,4′-tetrahydroxybenzylcoumaranone by DPPH assay

[0341] A 70 μM stock solution of 2,2-diphenyl-1-picrylhydrazyl (DPPH) inethanol was prepared. Such amounts of4,6,3′,4′-tetrahydroxybenzylcoumaranone (THBC) were added to aliquots ofthis solution so as to give the THBC/DPPH ratios indicated in Table 1.The absorbance was in each case measured at 515 nm, 25° C. and 1 cm,with Table 1 in each case indicating the value measured at constantabsorbance. The values are plotted graphically against one another inFIG. 1, with the molar ratio being plotted on the x axis and themeasured absorbance as a relative proportion of the absorbance measuredfor the stock solution (100%) being plotted on the y axis.

[0342] The EC₅₀ determined was 0.17. The concentration of test substanceemployed at the EC₅₀ value was 8.7 pmol.

[0343] Using the same experimental set-up, an EC₅₀ of 0.21 wasdetermined for tocopherol. 4,6,3′,4′-Tetrahydroxycoumaranone is thus amore potent antioxidant than tocopherol (vitamin E). TABLE 1 Absorbancedetermination in the DPPH assay Absorbance in %, based on THBC/DPPHabsorbance without THBC 0 100 0.01 97.66 0.02 94.04 0.05 87.02 0.0779.15 0.10 72.13 0.12 62.72 0.18 44.18 0.24 26.08 0.30 16.16 0.37 15.730.43 15.27 0.49 15.27 0.55 15.27 0.61 15.05 0.73 14.19 0.97 14.56 1.2114.56

EXAMPLE 15

[0344] O/W emulsion % by wt. Stearic acid 1.50 Glyceryl stearate SE 3.50Caprylic acid/capric acid triglyceride 5.00 Octyldodecanol 5.00 Dicaprylether 5.00 Cetylstearyl alcohol 0.50 Xanthan gum 0.50 Octyltriazone 0.50MBTTBP 6.00 Titanium dioxide 2.00 α-Glycosylrutin 0.20 Glycerol 3.00Sodium hydroxide solution, 45% 0.03 THBC 0.10 Ectoin 1.00 Preservative0.50 Water to 100.00

EXAMPLE 16

[0345] O/W emulsion % by wt. Stearic acid 1.50 Glyceryl stearate SE 3.50Caprylic acid/capric acid triglyceride 9.00 Octyldodecanol 9.00Dicaprylyl ether 9.00 Cetylstearyl alcohol 0.50 Xanthan gum 0.50Dibenzoylmethane 2.00 Methylbenzylidenecamphor 4.00 Boron nitride 0.50α-Glycosylrutin 0.50 Glycerol 5.00 Sodium hydroxide solution, 45% 0.03THBC 0.20 HMLO 0.30 EDTA solution 1.00 Preservative 0.50 Water to 100.00

EXAMPLE 17

[0346] O/W emulsion % by wt. Sorbitan stearate 2.00 Polyglyceryl3-methylglucose distearate 4.00 Caprylic acid/capric acid triglyceride5.00 Octyldodecanol 5.00 Dicaprylyl ether 5.00 Xanthan gum 0.50Octyltriazone 2.00 Uvasorb HEB 8.00 THBC 0.35 HMLO 0.10 Glycerol 3.00Phenylbenzimidazolesulfonic acid 2.00 Sodium hydroxide solution, 45%0.70 Ectoin 2.00 Preservative 0.50 Water to 100.00

EXAMPLE 18

[0347] O/W emulsion % by wt. Sorbitan stearate 2.00 Polyglyceryl3-methylglucose distearate 4.00 Caprylic acid/capric acid triglyceride5.00 Octyldodecanol 5.00 Dicaprylyl ether 5.00 Xanthan gum 0.50Dibenzoylmethane 2.00 Methylbenzylidenecamphor 4.00 THBC sulfate 0.20Boron nitride 1.00 Ectoin 2.00 Glycerol 5.00 Phenylbenzimidazolesulfonicacid 1.00 Sodium hydroxide solution, 45% 0.35 EDTA solution 1.00Preservative 0.50 Water to 100.00

EXAMPLE 19

[0348] O/W emulsion % by wt. Butylene glycol dicaprylate/dicaproate10.00  Shea butter 0.50 Phenyltrimethicone 2.00 Acrylate/C₁₀₋₃₀-alkylacrylate crosspolymer 0.50 Xanthan gum 0.50 T 150 3.00 α-Glycosylrutin1.20 THBC sulfate 0.30 Ectoin 0.10 Glycerol 3.00 Citric acid 0.40 Sodiumhydroxide solution, 45% 0.15 Preservative 0.50 Water to 100.00

EXAMPLE 20

[0349] Hydrodispersion % by wt. Butylene glycol dicaprylate/dicaproate10.00  Shea butter 0.50 Phenyltrimethicone 2.00 Acrylate/C₁₀₋₃₀-alkylacrylate crosspolymer 0.50 Xanthan gum 0.50 Dibenzoylmethane 1.00Methylbenzylidenecamphor 2.00 Uvasorb HEB 4.00 THBC 0.30 5-Hydroxyectoin1.00 Glycerol 3.00 Citric acid 0.40 Sodium hydroxide solution, 45% 0.15EDTA solution 1.00 Preservative 0.50 Water to 100.00

EXAMPLE 21

[0350] W/O emulsion % by wt. Glyceryl lanolate 1.00 Polyglyceryl2-dipolyhydroxystearate 4.00 Mineral oil 8.00 Butylene glycoldicaprylated/dicaproate 12.00  Isohexadecane 6.00 Dibenzoylmethane 1.00Methylbenzylidenecamphor 2.00 MBTTBP 4.00 THBC 0.20 Boron nitride 2.00Titanium dioxide 2.00 Glycerol 5.00 Magnesium sulfate 0.70 EDTA solution1.00 Preservative 0.50 Water to 100.00

EXAMPLE 22

[0351] W/O emulsion % by wt. Glyceryl lanolate 1.00 Polyglyceryl2-dipolyhydroxystearate 5.00 Mineral oil 8.00 Butylene glycoldicaprylate/dicaproate 12.00  Isohexadecane 6.00 THBC 0.50 Glycerol 3.00Magnesium sulfate 0.70 Preservative 0.50 Water to 100.00

EXAMPLE 23

[0352] W/O emulsion % by wt. PEG 30 dipolyhydroxystearate 4.00 Mineraloil 9.00 Butylene glycol dicaprylate/dicaproate 9.00 C₁₂₋₁₅-Alkylbenzoate 9.00 Dibenzoylmethane 2.00 Methylbenzylidenecamphor 4.00 MBTTBP4.00 THBC sulfate 0.50 α-Glycosylrutin 0.50 Glycerol 3.00 Magnesiumsulfate 0.70 EDTA solution 1.00 Preservative 0.50 Water to 100.00

EXAMPLE 24

[0353] W/O emulsion % by wt. PEG 30 dipolyhydroxystearate 4.00 Mineraloil 9.00 Butylene glycol dicaprylate/dicaproate 9.00 C₁₂₋₁₅-Alkylbenzoate 9.00 Ectoin 0.10 T 150 3.00 Uvasorb HEB 2.00 Octocrylene 10.00 THBC 0.05 Boron nitride 2.00 Titanium dioxide 2.00 Glycerol 3.00Magnesium sulfate 0.70 Preservative 0.50 Water to 100.00

EXAMPLE 25

[0354] W/O emulsion % by wt. Cetyldimethicone copolyol 4.00 Mineral oil9.00 Butylene glycol dicaprylate/dicaproate 9.00 C₁₂₋₁₅-Alkyl benzoate9.00 Dibenzoylmethane 2.00 Methylbenzylidenecamphor 4.00 5-Hydroxyectoin5.00 THBC 0.20 Glycerol 5.00 Magnesium sulfate 0.70 EDTA solution 1.00Preservative 0.50 Water to 100.00

EXAMPLE 26

[0355] W/O emulsion % by wt. Cetyldimethicone copolyol 3.00 Mineral oil9.00 Butylene glycol dicaprylate/dicaproate 9.00 C₁₂₋₁₅₋Alkyl benzoate9.00 Ectoin 0.05 THBC sulfate 0.50 Glycerol 3.00 Magnesium sulfate 0.70EDTA solution 1.00 Preservative 0.50 Water to 100.00

EXAMPLE 27

[0356] O/W emulsion % by wt. Stearic acid 1.50 Glycerol monostearate3.00 Caprylic acid/capric acid triglyceride 10.00  Dicaprylyl ether 5.00Dimethicone 2.00 Hydrogenated polyisobutene 2.00 Vitamin E acetate 0.50Ectoin 1.00 Tinosorb ® S 1.00 Methylbenzylidenecamphor 4.00 Titaniumdioxide 1.00 THBC 0.30 Quercetin 0.20 Preservative 0.50 Glycerol 3.00Xanthan gum 0.30 Sodium hydroxide solution, 45% 0.50 Water to 100.00

EXAMPLE 28

[0357] O/W emulsion % by wt. Sorbitan stearate 3.00 Polyglyceryl3-methylglucose distearate 1.50 Octyldodecanol 10.00  Dicaprylyl ether5.00 Mineral oil 5.00 Castor oil 2.00 Butylene glycoldicaprylate/caproate 5.00 Vitamin E acetate 0.50 Octocrylene 8.00Methylbenzylidenecamphor 4.00 Butylmethoxydibenzoylmethane 3.00 THBCsulfate 0.20 Rutin (water-soluble) 0.50 Boron nitride 2.005-Hydroxyectoin 2.00 Preservative 0.50 Glycerol 10.00  Xanthan gum 0.20Pemulen ® TR1 0.10 Phenylbenzimidazolesulfonic acid 2.00 Sodiumhydroxide solution, 45% 1.20 Water to 100.00

EXAMPLE 29

[0358] W/O emulsion % by wt. Polyglyceryl 2-dipolyhydroxystearate 5.00Dimethicone 2.00 Mineral oil 5.00 Isohexadecane 5.00 Butylene glycoldicaprylate/caproate 10.00  C₁₂₋₁₅-Alkyl benzoate 7.00Dioctylbutamidotriazone 3.00 Methylbenzylidenecamphor 2.00Butylmethoxydibenzoylmethane 2.00 Titanium dioxide 4.00 THBC 0.20 Rutin(water-soluble) 0.30 5-Hydroxyectoin 0.05 Preservative 0.50 Glycerol5.00 MgSO₄ 1.00 Water to 100.00

EXAMPLE 30

[0359] W/O emulsion % by wt. PEG 30 dipolyhydroxystearate 4.00 Caprylicacid/capric acid triglyceride 5.00 Octyldodecanol 5.00 Dicaprylyl ether5.00 Mineral oil 5.00 Isohexadecane 2.00 Hydrogenated polyisobutene 5.00C₁₂₋₁₄-Alkyl benzoate 10.00  Vitamin E acetate 0.50 Aerosil ® 972 0.50Ectoin 5.00 THBC sulfate 0.20 Rutin (water-soluble) 0.30 Preservative0.50 Glycerol 10.00  MgSO₄ 1.00 Water to 100.00

EXAMPLE 31

[0360] W/O emulsion % by wt. Cetyldimethicone copolyol 5.00 Dimethicone5.00 Mineral oil 2.00 Isohexadecane 2.00 Butylene glycoldicaprylate/caproate 5.00 C₁₂₋₁₅-Alkyl benzoate 5.00 Tinosorb ® S 3.00Octocrylene 4.00 Methylbenzylidenecamphor 4.00Butylmethoxydibenzoylmethane 2.00 Titanium dioxide 2.00 THBC 0.30Troxerutin 0.20 Boron nitride 4.00 5-Hydroxyectoin 0.05 Preservative0.50 Glycerol 5.00 NaCl 1.00 Sodium hydroxide solution, 45% 1.30 Waterto 100.00

EXAMPLE 32

[0361] Hydrodispersion % by wt. Caprylic acid/capric acid triglyceride10.00  Octyldodecanol 5.00 Dicaprylyl ether 2.00 Dimethicone 1.00Vitamin E acetate 0.50 Octyltriazone 2.00 Methylbenzylidenecamphor 4.00Butylmethoxydibenzoylmethane 2.00 Titanium dioxide 1.00 THBC 1.00Troxerutin 0.20 Ectoin 5.00 Preservative 0.50 Glycerol 3.00 Xanthan gum0.40 Pemulen ® TR1 0.40 Water to 100.00

EXAMPLE 33

[0362] W/O emulsion % by wt. Caprylic acid/capric acid triglyceride15.00 Hydrogenated polyisobutene 5.00 C₁₂₋₁₅-Alkyl benzoate 5.00Dioctylbutamidotriazone 2.00 Octyltriazone 2.00 Titanium dioxide 4.00Aerosil ® R 972 2.00 THBC sulfate 0.50 Troxerutin 0.20 Boron nitride1.00 Ectoin 1.00 Preservative 0.50 Glycerol 5.00 NaCl 1.00 Water to100.00

EXAMPLE 34

[0363] Spray % by wt. Glycerol monostearate 4.00 Ceteareth-12 1.50Caprylic acid/capric acid triglyceride 2.00 Mineral oil 5.00 Octocrylene6.00 Ectoin 0.05 THBC sulfate 0.20 Preservative 0.50 Glycerol 10.00 Phenylbenzimidazolesulfonic acid 1.00 Sodium hydroxide solution, 45%0.40 Water to 100.00

EXAMPLE 35

[0364] Spray % by wt. Glycerol monostearate SE 4.50 Ceteareth-20 1.00Dicaprylyl ether 5.00 Cetylstearyl isononanoate 5.00 Dimethicone 2.00Dioctylbutamidotriazone 1.00 Tinosorb ® S 1.00 Ectoin 1.00 THBC sulfate0.10 Boron nitride 1.00 Preservative 0.50 Glycerol 5.00 Water to 100.00

1. Cosmetic or pharmaceutical formulation comprising at least onecompound of the formula I

in which —X— is a single bond, —CH₂—, ═CH—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—,—CH(NR⁵R⁶)— or —CH(OR⁵)—, and R¹, R², R³, R⁴, R⁵ and R⁶ may be identicalor different and are, independently of one another, H straight-chain orbranched C₁- to C₁₂-alkyl and/or alkylcarbonyl groups, straight-chain orbranched C₃- to C₁₂-alkenyl and/or -alkenyl-carbonyl groups,straight-chain or branched C₁- to C₁₂-hydroxyalkyl groups, in which thehydroxyl group may be bonded to a primary or secondary carbon atom ofthe chain, and furthermore the alkyl chain may also be interrupted byoxygen, C₃- to C₁₀-cycloalkyl and/or cycloalkylcarbonyl groups and C₃-to C₁₂-cycloalkenyl and/or cycloalkenylcarbonyl groups, in which each ofthe rings may also be bridged by —(CH₂)_(n)— groups, where n=from 1 to3, aryl and/or arylcarbonyl groups, heteroaryl and/or heteroarylcarbonylgroups, where these groups may be substituted by alkyl, hydroxyl,alkoxy, amino, mono- and dialkylamino, sulfonic acid, carboxyl and/orhalogen groups, mono- and/or oligoglycosyl radicals,

 in which Me is a proton or an alkali metal ion, in particular a sodiumor potassium ion.
 2. Cosmetic or pharmaceutical formulation according toclaim 1, in which —X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—,—C(NR⁵)—, —CH(NR⁵R⁶)— or —CH(OR⁵)—.
 3. Cosmetic or pharmaceuticalformulation according to claim 1, in which —X— is ═CH— and at least oneradical from R¹, R², R³ and R⁴ is a group selected from the followinglist: straight-chain or branched C₁- to C₁₂-alkylcarbonyl groups,straight-chain or branched C₃- to C₁₂-alkenylcarbonyl groups,straight-chain or branched C₁- to C₁₂-hydroxyalkyl groups, in which thehydroxyl group may be bonded to a primary or secondary carbon atom ofthe chain, and furthermore the alkyl chain may also be interrupted byoxygen, C₃- to C₁₀-cycloalkylcarbonyl groups and C₃- to C₁₂-cycloalkenyland/or cycloalkenylcarbonyl groups, in which each of the rings may alsobe bridged by —(CH₂)_(n)— groups, where n=from 1 to 3, aryl and/orarylcarbonyl groups, heteroaryl and/or heteroarylcarbonyl groups, wherethese groups may be substituted by alkyl, hydroxyl, alkoxy, amino, mono-and dialkylamino, sulfonic acid, carboxyl and/or halogen groups, mono-and/or oligoglycosyl radicals,

in which Me is a proton or an alkali metal ion, in particular a sodiumor potassium ion.
 4. Cosmetic or pharmaceutical formulation according toat least one of the preceding claims, where the compound of the formulaI is 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one (X ═—CH₂— andR¹═R²═R³═R⁴═H) or a derivative thereof, preferably the trisulfate (X═—CH₂—; R₁═R³═R⁴═SO₃Me, R²═H).
 5. Cosmetic or pharmaceutical formulationaccording to at least one of the preceding claims, where the formulationcomprises one or more UV filters, which are preferably selected from thegroup consisting of 3-(4′-methylbenzylidine)-d 1-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium andtriethanolamine salts.
 6. Cosmetic or pharmaceutical formulationaccording to at least one of the preceding claims for protecting bodycells against oxidative stress, in particular for reducing skin ageing,which preferably comprises one or more antioxidants.
 7. Cosmetic orpharmaceutical formulation according to at least one of the precedingclaims, characterised in that the formulation comprises furtherskin-protecting or skin-care active ingredients, preferablypyrimidinecarboxylic acids of the formula II

in which R¹ is a radical H or C1-8-alkyl, R² is a radical H orC1-4-alkyl, and R³, R⁴, R⁵ and R⁶ are each, independently of oneanother, a radical from the group consisting of H, OH, NH₂ andC1-4-alkyl, and/or aryl oximes, in particular2-hydroxy-5-methyllaurophenone oxime.
 8. Cosmetic or pharmaceuticalformulation according to claim 7, characterised in thatpyrimidinecarboxylic acids of the formula II are present in which R² isa methyl or ethyl group, and R¹ or R⁵ and R⁶ are H, where at least oneof the pyrimidinecarboxylic acids is preferably ectoin((S)-1,4,5,6-tetrahydro-2-methyl4-pyrimidinecarboxylic acid) orhydroxyectoin ((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid).9. Cosmetic or pharmaceutical formulation according to at least one ofthe preceding claims, characterised in that the formulation is anemulsion which comprises O/W or W/O emulsifiers, with preferred W/Oemulsifiers being selected from glyceryl monostearate, glycerylmonoisostearate, glyceryl monomyristate, glyceryl monooleate,di-glyceryl monostearate, diglyceryl monoisostearate, propylene glycolmonostearate, propylene glycol monoisostearate, propylene glycolmonocaprylate, propylene glycol monolaurate, sorbitan monoisostearate,sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate,sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol,behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol,polyethylene glycol (2) stearyl ether (steareth-2), glycerylmonolaurate, glyceryl monocaprinate, glyceryl monocaprylate. 10.Cosmetic or pharmaceutical formulation according to at least one of thepreceding claims, characterised in that the formulation comprises atleast one hydrophilic surfactant, preferably selected from the groupconsisting of the alkyl glycosides, acyl lactylates, betaines andcoconut amphoacetates.
 11. Food comprising at least one compound of theformula I, where the variables are as defined in claim
 1. 12. Foodaccording to claim 11, further comprising vitamin C and/or a vitamin Cderivative.
 13. Compounds of the formula I, where the variables are asdefined in claim 2, as medicaments.
 14. Compounds of the formula I,where the variables are as defined in claim 3, as medicaments.
 15. Useof a compound of the formula I, where the variables are as defined inclaim 2, for the preparation of a medicament against oxidative stress,in particular for reducing skin ageing.
 16. Use of a compound of theformula I, where the variables are as defined in claim 2, for thepreparation of a medicament for the treatment of inflammation orallergic reactions.
 17. Compound of the formula I

where the variables are as defined in claim 1, characterised in that atleast one radical from R₁, R², R³ and R⁴ is not H.
 18. Compoundaccording to claim 17, characterised in that at least one radical fromR¹, R², R³ and R⁴ is an —SO₃Me or —PO₃Me₂ group, this compoundparticularly preferably being a compound of the formula III

which may be in pure form or in the form of a mixture with thecorresponding mono- and disulfates, particular preference being given tothe trisulfate of 4,6,3′,4′-tetrahydroxybenzylcoumaran-3-one. 19.Compound according to at least one of claims 17 and 18, characterised inthat —X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—,—CH(NR⁵R⁶)— or —CH(OR⁵)—.
 20. Use of compounds of the formula I in which—X— is a single bond, —CH₂—, —C(O)—, ═C(OR⁵)—, —C(NR⁵)—, —CH(NR⁵R⁶)— or—CH(OR⁵)—, and the other variables are as defined in claim 1, as anantioxidant, in particular for cosmetic formulations or foods.
 21. Useof a compound of the formula I in which —X— is a single bond, —CH₂—,—C(O)—, =C(OR⁵)—, —C(NR⁵)—, —CH(NR⁵R⁶)— or —CH(OR⁵)— and the othervariables are as defined in claim 1, for the stabilisation of UVfilters, in particular dibenzoylmethane and derivatives ofdibenzoylmethane.
 22. Use of formulations according to at least one ofclaims 1 to 10 or of compounds according to at least one of claims 17 to19 for immunoprotection.
 23. Use of formulations according to at leastone of claims 1 to 10 or of compounds according to at least one ofclaims 17 to 19 for DNA and RNA protection.
 24. Use of formulationsaccording to at least one of claims 1 to 10 or of compounds according toat least one of claims 17 to 19 for the protection of cells, inparticular of Langerhans cells.